@article{MTMT:33810653, title = {Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation}, url = {https://m2.mtmt.hu/api/publication/33810653}, author = {Chung, H.-L. and Ye, Q. and Park, Y.-J. and Zuo, Z. and Mok, J.-W. and Kanca, O. and Tattikota, S.G. and Lu, S. and Perrimon, N. and Lee, H.K. and Bellen, H.J.}, doi = {10.1016/j.cmet.2023.03.022}, journal-iso = {CELL METAB}, journal = {CELL METABOLISM}, volume = {35}, unique-id = {33810653}, issn = {1550-4131}, abstract = {VLCFAs (very-long-chain fatty acids) are the most abundant fatty acids in myelin. Hence, during demyelination or aging, glia are exposed to higher levels of VLCFA than normal. We report that glia convert these VLCFA into sphingosine-1-phosphate (S1P) via a glial-specific S1P pathway. Excess S1P causes neuroinflammation, NF-κB activation, and macrophage infiltration into the CNS. Suppressing the function of S1P in fly glia or neurons, or administration of Fingolimod, an S1P receptor antagonist, strongly attenuates the phenotypes caused by excess VLCFAs. In contrast, elevating the VLCFA levels in glia and immune cells exacerbates these phenotypes. Elevated VLCFA and S1P are also toxic in vertebrates based on a mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Indeed, reducing VLCFA with bezafibrate ameliorates the phenotypes. Moreover, simultaneous use of bezafibrate and fingolimod synergizes to improve EAE, suggesting that lowering VLCFA and S1P is a treatment avenue for MS. © 2023}, keywords = {lipid metabolism; MULTIPLE SCLEROSIS; neurodegeneration; neuroinflammation; sphingolipid; NF-κB activation; fingolimod; Sphingosine 1-phosphate; myelin lipid; VLCFA β-oxidation}, year = {2023}, eissn = {1932-7420}, pages = {855-874.e5} } @article{MTMT:34261528, title = {split-intein Gal4 provides intersectional genetic labeling that is repressible by Gal80}, url = {https://m2.mtmt.hu/api/publication/34261528}, author = {Ewen-Campen, Ben and Luan, Haojiang and Xua, Jun and Singh, Rohit and Joshi, Neha and Thakkar, Tanuj and Berger, Bonnie and White, Benjamin H. and Perrimon, Norbert}, doi = {10.1073/pnas.2304730120}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {120}, unique-id = {34261528}, issn = {0027-8424}, abstract = {The split-Gal4 system allows for intersectional genetic labeling of highly specific cell types and tissues in Drosophila. However, the existing split-Gal4 system, unlike the standard Gal4 system, cannot be repressed by Gal80, and therefore cannot be controlled temporally. This lack of temporal control precludes split-Gal4 experiments in which a genetic manipulation must be restricted to specific timepoints. Here, we describe a split-Gal4 system based on a self-excising split-intein, which drives transgene expression as strongly as the current split-Gal4 system and Gal4 reagents, yet which is repressible by Gal80. We demonstrate the potent inducibility of "split-intein Gal4" in vivo using both fluorescent reporters and via reversible tumor induction in the gut. Further, we show that our split-intein Gal4 can be extended to the drug-inducible GeneSwitch system, providing an independent method for intersectional labeling with inducible control. We also show that the split-intein Gal4 system can be used to generate highly cell type-specific genetic drivers based on in silico predictions generated by single-cell RNAseq (scRNAseq) datasets, and we describe an algorithm ("Two Against Background" or TAB) to predict cluster-specific gene pairs across multiple tissue-specific scRNA datasets. We provide a plasmid toolkit to efficiently create split-intein Gal4 drivers based on either CRISPR knock-ins to target genes or using enhancer fragments. Altogether, the split-intein Gal4 system allows for the creation of highly specific intersectional genetic drivers that are inducible/repressible.}, keywords = {DROSOPHILA; SINGLE-CELL TRANSCRIPTOMICS; intersectional genetics; split-Gal4}, year = {2023}, eissn = {1091-6490}, orcid-numbers = {Perrimon, Norbert/0000-0001-7542-472X} } @article{MTMT:34298309, title = {Single-cell transcriptomics identifies new blood cell populations in Drosophila released at the onset of metamorphosis}, url = {https://m2.mtmt.hu/api/publication/34298309}, author = {Hirschhaeuser, Alexander and Molitor, Darius and Salinas, Gabriela and Grosshans, Jorg and Rust, Katja and Bogdan, Sven}, doi = {10.1242/dev.201767}, journal-iso = {DEVELOPMENT}, journal = {DEVELOPMENT}, volume = {150}, unique-id = {34298309}, issn = {0950-1991}, abstract = {Drosophila blood cells called hemocytes form an efficient barrier against infections and tissue damage. During metamorphosis, hemocytes undergo tremendous changes in their shape and behavior, preparing them for tissue clearance. Yet, the diversity and functional plasticity of pupal blood cells have not been explored. Here, we combine single-cell transcriptomics and high-resolution microscopy to dissect the heterogeneity and plasticity of pupal hemocytes. We identified undifferentiated and specified hemocytes with different molecular signatures associated with distinct functions such as antimicrobial, antifungal immune defense, cell adhesion or secretion. Strikingly, we identified a highly migratory and immuneresponsive pupal cell population expressing typical markers of the posterior signaling center (PSC), which is known to be an important niche in the larval lymph gland. PSC-like cells become restricted to the abdominal segments and are morphologically very distinct from experiments further suggest that PSC-like cells can transdifferentiate to lamellocytes triggered by parasitoid wasp infestation. In summary, we present the first molecular description of pupal Drosophila blood cells, providing insights into blood cell functional diversification and plasticity during pupal metamorphosis.}, keywords = {BLOOD; DROSOPHILA; HEMOCYTES; MIGRATION; PROGENITOR; PSC; lamellocytes; plasmatocytes; scRNA-seq analysis}, year = {2023}, eissn = {1477-9129}, orcid-numbers = {Molitor, Darius/0000-0001-5998-4014; Grosshans, Jorg/0000-0003-1114-9233; Bogdan, Sven/0000-0002-8753-9855} } @article{MTMT:34576395, title = {The human leukemic oncogene MLL-AF4 promotes hyperplastic growth of hematopoietic tissues in Drosophila larvae}, url = {https://m2.mtmt.hu/api/publication/34576395}, author = {Johannessen, J.A. and Formica, M. and Haukeland, A.L.C. and Bråthen, N.R. and Al, Outa A. and Aarsund, M. and Therrien, M. and Enserink, J.M. and Knævelsrud, H.}, doi = {10.1016/j.isci.2023.107726}, journal-iso = {ISCIENCE}, journal = {ISCIENCE}, volume = {26}, unique-id = {34576395}, abstract = {MLL-rearranged (MLL-r) leukemias are among the leukemic subtypes with poorest survival, and treatment options have barely improved over the last decades. Despite increasing molecular understanding of the mechanisms behind these hematopoietic malignancies, this knowledge has had poor translation into the clinic. Here, we report a Drosophila melanogaster model system to explore the pathways affected in MLL-r leukemia. We show that expression of the human leukemic oncogene MLL-AF4 in the Drosophila hematopoietic system resulted in increased levels of circulating hemocytes and an enlargement of the larval hematopoietic organ, the lymph gland. Strikingly, depletion of Drosophila orthologs of known interactors of MLL-AF4, such as DOT1L, rescued the leukemic phenotype. In agreement, treatment with small-molecule inhibitors of DOT1L also prevented the MLL-AF4-induced leukemia-like phenotype. Taken together, this model provides an in vivo system to unravel the genetic interactors involved in leukemogenesis and offers a system for improved biological understanding of MLL-r leukemia. © 2023 The Author(s)}, keywords = {Oncology; Molecular Biology; CELL BIOLOGY}, year = {2023}, eissn = {2589-0042} } @article{MTMT:33555087, title = {A Novel Method for Primary Blood Cell Culturing and Selection in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/33555087}, author = {Kúthy-Sutus, Enikő and Kharrat, Bayan and Gábor, Erika and Csordás, Gábor and Sinka, Rita and Honti, Viktor}, doi = {10.3390/cells12010024}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {12}, unique-id = {33555087}, abstract = {The blood cells of the fruit fly Drosophila melanogaster show many similarities to their vertebrate counterparts, both in their functions and their differentiation. In the past decades, a wide palette of immunological and transgenic tools and methods have been developed to study hematopoiesis in the Drosophila larva. However, the in vivo observation of blood cells is technically restricted by the limited transparency of the body and the difficulty in keeping the organism alive during imaging. Here we describe an improved ex vivo culturing method that allows effective visualization and selection of live blood cells in primary cultures derived from Drosophila larvae. Our results show that cultured hemocytes accurately represent morphological and functional changes following immune challenges and in case of genetic alterations. Since cell culturing has hugely contributed to the understanding of the physiological properties of vertebrate blood cells, this method provides a versatile tool for studying Drosophila hemocyte differentiation and functions ex vivo.}, year = {2023}, eissn = {2073-4409}, orcid-numbers = {Kúthy-Sutus, Enikő/0000-0002-1398-4120; Csordás, Gábor/0000-0001-6871-6839; Sinka, Rita/0000-0003-4040-4184} } @article{MTMT:32524824, title = {Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids}, url = {https://m2.mtmt.hu/api/publication/32524824}, author = {Cinege, Gyöngyi Ilona and Magyar, Lilla Brigitta and Kovács, Attila Lajos and Lerner, Zita and Juhász, Gábor and Lukacsovich, David and Winterer, Jochen and Lukacsovich, Tamás and Hegedűs, Zoltán and Kurucz, Judit Éva and Hultmark, Dan and Földy, Csaba and Andó, István}, doi = {10.1159/000520110}, journal-iso = {J INNATE IMMUN}, journal = {JOURNAL OF INNATE IMMUNITY}, volume = {14}, unique-id = {32524824}, issn = {1662-811X}, year = {2022}, eissn = {1662-8128}, pages = {335-354}, orcid-numbers = {Juhász, Gábor/0000-0001-8548-8874; Winterer, Jochen/0000-0002-6800-6594; Lukacsovich, Tamás/0000-0001-5908-9861; Hultmark, Dan/0000-0002-6506-5855; Andó, István/0000-0002-4648-9396} } @article{MTMT:33181626, title = {Single-cell RNA-seq uncovered hemocyte functional subtypes and their differentiational characteristics and connectivity with morphological subpopulations in Litopenaeus vannamei}, url = {https://m2.mtmt.hu/api/publication/33181626}, author = {Cui, Chuang and Tang, Xiaoqian and Xing, Jing and Sheng, Xiuzhen and Chi, Heng and Zhan, Wenbin}, doi = {10.3389/fimmu.2022.980021}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {33181626}, issn = {1664-3224}, abstract = {Hemocytes play central roles in shrimp immune system, whereas whose subclasses have not yet been completely defined. At present, the morphological classification of hemocytes is inadequate to classify the complete hemocyte repertoire and elucidate the functions and differentiation and maturation processes. Based on single-cell RNA sequencing (scRNA-seq) of hemocytes in healthy Litopenaeus vannamei, combined with RNA-FISH and flow cytometric sorting, we identified three hemocyte clusters including TGase(+) cells, CTL+ cells and Crustin(+) cells, and further determined their functional properties, potential differentiation trajectory and correspondence with morphological subpopulations. The TGase(+) cells were mainly responsible for the coagulation, exhibiting distinguishable characteristics of hyalinocyte, and appeared to be developmentally arrested at an early stage of hemocyte differentiation. The CTL+ cells and Crustin(+) cells arrested at terminal stages of differentiation mainly participated in recognizing foreign pathogens and initiating immune defense responses, owning distinctive features of granule-containing hemocytes. Furthermore, we have revealed the functional sub-clusters of three hemocyte clusters and their potential differentiation pathways according to the expression of genes involved in cell cycle, cell differentiation and immune response, and the successive differentiation and maturation of hyalinocytes to granule-containing hemocytes have also mapped. The results revealed the diversity of shrimp hemocytes and provide new theoretical rationale for hemocyte classification, which also facilitate systematic research on crustacean immunity.}, keywords = {HEMOCYTES; Litopenaeus vannamei; Single-cell RNA-seq; differentiation trajectory; functional cluster}, year = {2022}, eissn = {1664-3224} } @article{MTMT:33810657, title = {Trans-regulatory changes underpin the evolution of the Drosophila immune response}, url = {https://m2.mtmt.hu/api/publication/33810657}, author = {Ding, S.D. and Leitão, A.B. and Day, J.P. and Arunkumar, R. and Phillips, M. and Zhou, S.O. and Jiggins, F.M.}, doi = {10.1371/journal.pgen.1010453}, journal-iso = {PLOS GENET}, journal = {PLOS GENETICS}, volume = {18}, unique-id = {33810657}, issn = {1553-7390}, abstract = {When an animal is infected, the expression of a large suite of genes is changed, resulting in an immune response that can defend the host. Despite much evidence that the sequence of proteins in the immune system can evolve rapidly, the evolution of gene expression is comparatively poorly understood. We therefore investigated the transcriptional response to parasitoid wasp infection in Drosophila simulans and D. sechellia. Although these species are closely related, there has been a large scale divergence in the expression of immune-responsive genes in their two main immune tissues, the fat body and hemocytes. Many genes, including those encoding molecules that directly kill pathogens, have cis regulatory changes, frequently resulting in large differences in their expression in the two species. However, these changes in cis regulation overwhelmingly affected gene expression in immune-challenged and uninfected animals alike. Divergence in the response to infection was controlled in trans. We argue that altering trans-regulatory factors, such as signalling pathways or immune modulators, may allow natural selection to alter the expression of large numbers of immune-responsive genes in a coordinated fashion. Copyright: © 2022 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.}, keywords = {Animals; GENETICS; ARTICLE; signal transduction; DROSOPHILA; DROSOPHILA; animal; controlled study; nonhuman; Evolution, Molecular; Species Specificity; Immunity; Immunity; species difference; regulatory mechanism; Gene Expression; natural selection; human cell; protein expression; immune response; blood cell; molecular evolution; genetic transcription; Drosophila Proteins; Parasitoid; Drosophila protein; WASP; FAT PAD; infectious agent; Drosophila simulans}, year = {2022}, eissn = {1553-7404} } @article{MTMT:33039275, title = {Hematopoietic plasticity mapped in Drosophila and other insects}, url = {https://m2.mtmt.hu/api/publication/33039275}, author = {Hultmark, Dan and Andó, István}, doi = {10.7554/eLife.78906}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {11}, unique-id = {33039275}, issn = {2050-084X}, year = {2022}, eissn = {2050-084X}, orcid-numbers = {Hultmark, Dan/0000-0002-6506-5855; Andó, István/0000-0002-4648-9396} } @article{MTMT:33050458, title = {Peeling Back the Layers of Lymph Gland Structure and Regulation}, url = {https://m2.mtmt.hu/api/publication/33050458}, author = {Kharrat, Bayan and Csordás, Gábor and Honti, Viktor}, doi = {10.3390/ijms23147767}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33050458}, issn = {1661-6596}, abstract = {During the past 60 years, the fruit fly, Drosophila melanogaster, has proven to be an excellent model to study the regulation of hematopoiesis. This is not only due to the evolutionarily conserved signalling pathways and transcription factors contributing to blood cell fate, but also to convergent evolution that led to functional similarities in distinct species. An example of convergence is the compartmentalization of blood cells, which ensures the quiescence of hematopoietic stem cells and allows for the rapid reaction of the immune system upon challenges. The lymph gland, a widely studied hematopoietic organ of the Drosophila larva, represents a microenvironment with similar features and functions to classical hematopoietic stem cell niches of vertebrates. Lymph gland studies were effectively supported by the unparalleled toolkit developed in Drosophila, which enabled the high-resolution investigation of the cellular composition and regulatory interaction networks of the lymph gland. In this review, we summarize how our understanding of lymph gland structure and hematopoietic cell-to-cell communication evolved during the past decades and compare their analogous features to those of the vertebrate hematopoietic stem cell niche.}, keywords = {IMMUNE-RESPONSE; DROSOPHILA; matrix protein; Hematopoiesis; SELF-RENEWAL; HEMATOPOIETIC STEM-CELL; Biochemistry & Molecular Biology; HSC; N-cadherin; lymph gland; EMBRYONIC ORIGIN; Drosophila larvae; PROGENITOR MAINTENANCE; HEMOCYTE LINEAGES}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839} } @article{MTMT:32971817, title = {Fat body-derived Spz5 remotely facilitates tumor-suppressive cell competition through Toll-6-a-Spectrin axis-mediated Hippo activation}, url = {https://m2.mtmt.hu/api/publication/32971817}, author = {Kong, Du and Zhao, Sihua and Xu, Wenyan and Dong, Jinxi and Ma, Xianjue}, doi = {10.1016/j.celrep.2022.110980}, journal-iso = {CELL REP}, journal = {CELL REPORTS}, volume = {39}, unique-id = {32971817}, issn = {2211-1247}, abstract = {Tumor-suppressive cell competition is an evolutionarily conserved process that selectively removes precancerous cells to maintain tissue homeostasis. Using the polarity-deficiency-induced cell competition model in Drosophila, we identify Toll-6, a Toll-like receptor family member, as a driver of tension-mediated cell competition through a-Spectrin (a-Spec)-Yorkie (Yki) cascade. Toll-6 aggregates along the boundary between wild type and polarity-deficient clones, where Toll-6 physically interacts with the cytoskeleton network protein a-Spec to increase mechanical tension, resulting in actomyosin-dependent Hippo pathway activation and the elimination of scrib mutant cells. Furthermore, we show that Spz5 secreted from fat body, the key innate organ in fly, facilitates the elimination of scrib clones by binding to Toll-6. These findings uncover mechanisms by which fat bodies remotely regulate tumor-suppressive cell competition of polarity-deficient tumors through inter-organ crosstalk and identified the Toll-6-a-Spec axis as an essential guardian that prevents tumorigenesis via tension-mediated cell elimination.}, year = {2022}, eissn = {2211-1247} } @article{MTMT:32971818, title = {Article Toll-9 interacts with Toll-1 to mediate a feedback loop during apoptosis-induced proliferation in Drosophila}, url = {https://m2.mtmt.hu/api/publication/32971818}, author = {Shields, Alicia and Amcheslavsky, Alla and Brown, Elizabeth and Lee, Tom V. and Nie, Yingchao and Tanji, Takahiro and Ip, Y. Tony and Bergmann, Andreas}, doi = {10.1016/j.celrep.2022.110817}, journal-iso = {CELL REP}, journal = {CELL REPORTS}, volume = {39}, unique-id = {32971818}, issn = {2211-1247}, abstract = {Drosophila Toll-1 and all mammalian Toll-like receptors regulate innate immunity. However, the functions of the remaining eight Toll-related proteins in Drosophila are not fully understood. Here, we show that Drosophila Toll-9 is necessary and sufficient for a special form of compensatory proliferation after apoptotic cell loss (undead apoptosis-induced proliferation [AiP]). Mechanistically, for AiP, Toll-9 interacts with Toll-1 to activate the intracellular Toll-1 pathway for nuclear translocation of the NF-KB-like transcription factor Dorsal, which induces expression of the pro-apoptotic genes reaper and hid. This activity contributes to the feedback amplification loop that operates in undead cells. Given that Toll-9 also functions in loser cells during cell competition, we define a general role of Toll-9 in cellular stress situations leading to the expression of proapoptotic genes that trigger apoptosis and apoptosis-induced processes such as AiP. This work identifies conceptual similarities between cell competition and AiP.}, year = {2022}, eissn = {2211-1247} } @article{MTMT:33658441, title = {Hemocytes are essential for Drosophila melanogaster post-embryonic development, independent of control of the microbiota}, url = {https://m2.mtmt.hu/api/publication/33658441}, author = {Stephenson, Holly N. and Streeck, Robert and Grublinger, Florian and Goosmann, Christian and Herzig, Alf}, doi = {10.1242/dev.200286}, journal-iso = {DEVELOPMENT}, journal = {DEVELOPMENT}, volume = {149}, unique-id = {33658441}, issn = {0950-1991}, abstract = {Proven roles for hemocytes (blood cells) have expanded beyond the control of infections in Drosophila. Despite this, the crucial role of hemocytes in post-embryonic development has long thought to be limited to control of microorganisms during metamorphosis. This has previously been shown by rescue of adult development in hemocyteablation models under germ-free conditions. Here, we show that hemocytes have an essential role in post-embryonic development beyond their ability to control the microbiota. Using a newly generated strong hemocyte-specific driver line for the GAL4/UAS system, we show that specific ablation of hemocytes is early pupal lethal, even under axenic conditions. Genetic rescue experiments prove that this is a hemocyte-specific phenomenon. RNA-seq data suggests that dysregulation of the midgut is a prominent consequence of hemocyte ablation in larval stages, resulting in reduced gut lengths. Dissection suggests that multiple processes may be affected during metamorphosis. We believe this previously unreported role for hemocytes during metamorphosis is a major finding for the field.}, keywords = {SYSTEM; RECEPTOR; CELL; DROSOPHILA; HEMOCYTES; metamorphosis; expression analysis; REVEALS; RNA-Seq}, year = {2022}, eissn = {1477-9129}, orcid-numbers = {Stephenson, Holly N./0000-0002-8121-9252; Herzig, Alf/0000-0003-4246-4666} } @article{MTMT:33041863, title = {Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues}, url = {https://m2.mtmt.hu/api/publication/33041863}, author = {Yu, S. and Luo, F. and Xu, Y. and Zhang, Y. and Jin, L.H.}, doi = {10.3389/fimmu.2022.905370}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {33041863}, issn = {1664-3224}, abstract = {The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit fly Drosophila melanogaster employs multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi. Drosophila has been shown to be a powerful in vivo model for studying the mechanism of innate immunity and host-pathogen interactions because Drosophila and higher organisms share conserved signaling pathways and factors. Moreover, the ease with which Drosophila genetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated in Drosophila innate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration in Drosophila will help us better study human innate immunity-related diseases. Copyright © 2022 Yu, Luo, Xu, Zhang and Jin.}, keywords = {DROSOPHILA; innate immunity; immune response; SIGNALING PATHWAY; Tissue communication}, year = {2022}, eissn = {1664-3224} } @article{MTMT:31940120, title = {Immunoprofiling of Drosophila Hemocytes by Single-cell Mass Cytometry}, url = {https://m2.mtmt.hu/api/publication/31940120}, author = {Balog, József Ágoston and Honti, Viktor and Kurucz, Judit Éva and Kari, Beáta and Puskás, László and Andó, István and Szebeni, Gábor}, doi = {10.1016/j.gpb.2020.06.022}, journal-iso = {GENOM PROTEOM BIOINF}, journal = {GENOMICS PROTEOMICS & BIOINFORMATICS}, volume = {19}, unique-id = {31940120}, issn = {1672-0229}, year = {2021}, eissn = {2210-3244}, pages = {243-252}, orcid-numbers = {Andó, István/0000-0002-4648-9396; Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:32601830, title = {Characterization of the Drosophila Adult Hematopoietic System Reveals a Rare Cell Population With Differentiation and Proliferation Potential}, url = {https://m2.mtmt.hu/api/publication/32601830}, author = {Boulet, M. and Renaud, Y. and Lapraz, F. and Benmimoun, B. and Vandel, L. and Waltzer, L.}, doi = {10.3389/fcell.2021.739357}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {9}, unique-id = {32601830}, issn = {2296-634X}, abstract = {While many studies have described Drosophila embryonic and larval blood cells, the hematopoietic system of the imago remains poorly characterized and conflicting data have been published concerning adult hematopoiesis. Using a combination of blood cell markers, we show that the adult hematopoietic system is essentially composed of a few distinct mature blood cell types. In addition, our transcriptomics results indicate that adult and larval blood cells have both common and specific features and it appears that adult hemocytes reactivate many genes expressed in embryonic blood cells. Interestingly, we identify a small set of blood cells that does not express differentiation markers but rather maintains the expression of the progenitor marker domeMeso. Yet, we show that these cells are derived from the posterior signaling center, a specialized population of cells present in the larval lymph gland, rather than from larval blood cell progenitors, and that their maintenance depends on the EBF transcription factor Collier. Furthermore, while these cells are normally quiescent, we find that some of them can differentiate and proliferate in response to bacterial infection. In sum, our results indicate that adult flies harbor a small population of specialized cells with limited hematopoietic potential and further support the idea that no substantial hematopoiesis takes place during adulthood. © Copyright © 2021 Boulet, Renaud, Lapraz, Benmimoun, Vandel and Waltzer.}, keywords = {DROSOPHILA; Hematopoiesis; imago; blood cell progenitor; Collier}, year = {2021}, eissn = {2296-634X} } @article{MTMT:32913577, title = {The cellular innate immune response of the invasive pest insect drosophila suzukii against pseudomonas entomophila involves the release of extracellular traps}, url = {https://m2.mtmt.hu/api/publication/32913577}, author = {Carrau, T. and Thümecke, S. and Silva, L.M.R. and Perez-Bravo, D. and Gärtner, U. and Taubert, A. and Hermosilla, C. and Vilcinskas, A. and Lee, K.-Z.}, doi = {10.3390/cells10123320}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {10}, unique-id = {32913577}, abstract = {Drosophila suzukii is a neobiotic invasive pest that causes extensive damage to fruit crops worldwide. The biological control of this species has been unsuccessful thus far, in part because of its robust cellular innate immune system, including the activity of professional phagocytes known as hemocytes and plasmatocytes. The in vitro cultivation of primary hemocytes isolated from D. suzukii third-instar larvae is a valuable tool for the investigation of hemocyte-derived effector mechanisms against pathogens such as wasp parasitoid larvae, bacteria, fungi and viruses. Here, we describe the morphological characteristics of D. suzukii hemocytes and evaluate early innate immune responses, including extracellular traps released against the entomopathogen Pseudomonas entomophila and lipopolysaccharides. We show for the first time that D. suzukii plasmatocytes cast extracellular traps to combat P. entomophila, along with other cell-mediated reactions, such as phagocytosis and the formation of filopodia. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.}, keywords = {Animals; metabolism; PHAGOCYTOSIS; ARTICLE; PHAGOCYTES; LIPOPOLYSACCHARIDE; LIPOPOLYSACCHARIDE; DROSOPHILA; DROSOPHILA; HEMOCYTES; HEMOCYTES; immunology; animal; Cell Survival; Cell Survival; MORPHOLOGY; physiology; innate immunity; controlled study; Cytology; nonhuman; larva; larva; microbiology; ultrastructure; drug effect; image analysis; scanning electron microscopy; cell culture; cell culture; Lipopolysaccharides; phagocyte; immune response; blood cell; Immunity, Innate; plasma cell; immunofluorescence; PSEUDOMONAS; PSEUDOMONAS; Cell viability; Histone; confocal microscopy; coculture; morphological trait; neomycin; biological pest control; Hemolymph; Parasitoid; Pseudopodia; Invasive pest; extracellular trap; extracellular trap; Extracellular Traps; Extracellular Traps; pseudopodium; plasmatocytes; Drosophila suzukii; Drosophila suzukii; introduced species; introduced species; Pest insect; Pseudomonas entomophila}, year = {2021}, eissn = {2073-4409} } @article{MTMT:32361808, title = {Identification of functionally distinct macrophage subpopulations in Drosophila}, url = {https://m2.mtmt.hu/api/publication/32361808}, author = {Coates, Jonathon Alexis and Brooks, Elliot and Brittle, Amy Louise and Armitage, Emma Louise and Zeidler, Martin Peter and Evans, Iwan Robert}, doi = {10.7554/eLife.58686}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {10}, unique-id = {32361808}, issn = {2050-084X}, abstract = {Vertebrate macrophages are a highly heterogeneous cell population, but while Drosophila blood is dominated by a macrophage-like lineage (plasmatocytes), until very recently these cells were considered to represent a homogeneous population. Here, we present our identification of enhancer elements labelling plasmatocyte subpopulations, which vary in abundance across development. These subpopulations exhibit functional differences compared to the overall population, including more potent injury responses and differential localisation and dynamics in pupae and adults. Our enhancer analysis identified candidate genes regulating plasmatocyte behaviour: pan-plasmatocyte expression of one such gene (Calnexin14D) improves wound responses, causing the overall population to resemble more closely the subpopulation marked by the Calnexin14D-associated enhancer. Finally, we show that exposure to increased levels of apoptotic cell death modulates subpopulation cell numbers. Taken together this demonstrates macrophage heterogeneity in Drosophila, identifies mechanisms involved in subpopulation specification and function and facilitates the use of Drosophila to study macrophage heterogeneity in vivo.}, year = {2021}, eissn = {2050-084X} } @article{MTMT:31743832, title = {There and back again: The mechanisms of differentiation and transdifferentiation in Drosophila blood cells}, url = {https://m2.mtmt.hu/api/publication/31743832}, author = {Csordás, Gábor and Gábor, Erika and Honti, Viktor}, doi = {10.1016/j.ydbio.2020.10.006}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {469}, unique-id = {31743832}, issn = {0012-1606}, year = {2021}, eissn = {1095-564X}, pages = {135-143}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839} } @article{MTMT:32361576, title = {Haemocyte-mediated immunity in insects: Cells, processes and associated components in the fight against pathogens and parasites}, url = {https://m2.mtmt.hu/api/publication/32361576}, author = {Eleftherianos, Ioannis and Heryanto, Christa and Bassal, Taha and Zhang, Wei and Tettamanti, Gianluca and Mohamed, Amr}, doi = {10.1111/imm.13390}, journal-iso = {IMMUNOLOGY}, journal = {IMMUNOLOGY}, volume = {164}, unique-id = {32361576}, issn = {0019-2805}, abstract = {The host defence of insects includes a combination of cellular and humoral responses. The cellular arm of the insect innate immune system includes mechanisms that are directly mediated by haemocytes (e.g., phagocytosis, nodulation and encapsulation). In addition, melanization accompanying coagulation, clot formation and wound healing, nodulation and encapsulation processes leads to the formation of cytotoxic redox-cycling melanin precursors and reactive oxygen and nitrogen species. However, demarcation between cellular and humoral immune reactions as two distinct categories is not straightforward. This is because many humoral factors affect haemocyte functions and haemocytes themselves are an important source of many humoral molecules. There is also a considerable overlap between cellular and humoral immune functions that span from recognition of foreign intruders to clot formation. Here, we review these immune reactions starting with the cellular mechanisms that limit haemolymph loss and participate in wound healing and clot formation and advancing to cellular functions that are critical in restricting pathogen movement and replication. This information is important because it highlights that insect cellular immunity is controlled by a multilayered system, different components of which are activated by different pathogens or during the different stages of the infection.}, keywords = {haematopoiesis; haemocytes; prophenoloxidase; autophagy and apoptosis; cytotoxic intermediates; insect cellular immunity}, year = {2021}, eissn = {1365-2567}, pages = {401-432}, orcid-numbers = {Eleftherianos, Ioannis/0000-0002-4822-3110; Mohamed, Amr/0000-0003-2788-5534} } @article{MTMT:32913579, title = {Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/32913579}, author = {Girard, J.R. and Goins, L.M. and Vuu, D.M. and Sharpley, M.S. and Spratford, C.M. and Mantri, S.R. and Banerjee, U.}, doi = {10.7554/eLife.67516}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {10}, unique-id = {32913579}, issn = {2050-084X}, abstract = {Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single cell RNA-Seq, and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, and inhibits canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis. © 2021, eLife Sciences Publications Ltd. All rights reserved.}, keywords = {Animals; Female; Female; Male; Male; metabolism; PHENOTYPE; GENETICS; immunohistochemistry; TRANSCRIPTION FACTOR; green fluorescent protein; DNA-BINDING PROTEINS; ARTICLE; ENDOCYTOSIS; DROSOPHILA; HEMOCYTES; stem cell; animal; Cell Differentiation; Genotype; growth, development and aging; reverse transcription polymerase chain reaction; controlled study; nonhuman; larva; larva; Flow Cytometry; Cell Cycle; Gene Expression; Drosophila melanogaster; Drosophila melanogaster; lipid; monoclonal antibody; blood cell; reactive oxygen metabolite; plasma cell; DNA binding protein; stress activated protein kinase; DNA Damage; extracellular matrix; phosphate buffered saline; Glycolysis; Citric Acid Cycle; reduced nicotinamide adenine dinucleotide phosphate; polyclonal antibody; chaperone; Isocitrate dehydrogenase; endosome; RNA extraction; cell heterogeneity; lymph node; RNA sequence; cell cycle S phase; Hematopoiesis; Hematopoiesis; fluorescence activated cell sorting; cell cycle progression; enhanced green fluorescent protein; cell suspension; collagen synthesis; synaptotagmin I; hydroxyproline; scatter factor; sphingolipid; Notch signaling; uvomorulin; Drosophila Proteins; Hemolymph; Hemolymph; protein Myb; Differential gene expression; Drosophila protein; hypoxia inducible factor; DNA damage checkpoint; MAPK signaling; RNA sequencing; pentose phosphate cycle; Juvenile hormone; PHOSPHOGLUCONATE DEHYDROGENASE; autophagy (cellular); Juvenile hormones; single cell RNA seq; small cytoplasmic RNA; numb protein, Drosophila; Sima protein, Drosophila; SiMa cell line}, year = {2021}, eissn = {2050-084X} } @article{MTMT:32913576, title = {CK1α protects WAVE from degradation to regulate cell shape and motility in the immune response}, url = {https://m2.mtmt.hu/api/publication/32913576}, author = {Hirschhäuser, A. and van, Cann M. and Bogdan, S.}, doi = {10.1242/jcs.258891}, journal-iso = {J CELL SCI}, journal = {JOURNAL OF CELL SCIENCE}, volume = {134}, unique-id = {32913576}, issn = {0021-9533}, abstract = {The WAVE regulatory complex (WRC) is the main activator of the Arp2/3 complex, promoting lamellipodial protrusions in migrating cells. The WRC is basally inactive but can be activated by Rac1 and phospholipids, and through phosphorylation. However, the in vivo relevance of the phosphorylation of WAVE proteins remains largely unknown. Here, we identified casein kinase I alpha (CK1α) as a regulator of WAVE, thereby controlling cell shape and cell motility in Drosophila macrophages. CK1α binds and phosphorylates WAVE in vitro. Phosphorylation of WAVE by CK1α appears not to be required for activation but, rather, regulates its stability. Pharmacologic inhibition of CK1α promotes ubiquitin-dependent degradation of WAVE. Consistently, loss of Ck1α but not ck2 function phenocopies the depletion of WAVE. Phosphorylation-deficient mutations in the CK1α consensus sequences within the VCA domain of WAVE can neither rescue mutant lethality nor lamellipodium defects. By contrast, phosphomimetic mutations rescue all cellular and developmental defects. Finally, RNAi-mediated suppression of 26S proteasome or E3 ligase complexes substantially rescues lamellipodia defects in CK1α-depleted macrophages. Therefore, we conclude that basal phosphorylation of WAVE by CK1α protects it from premature ubiquitin-dependent degradation, thus promoting WAVE function in vivo. © 2021. Published by The Company of Biologists Ltd}, keywords = {Humans; PHOSPHORYLATION; PHOSPHORYLATION; PHOSPHORYLATION; metabolism; MACROPHAGES; GENETICS; DROSOPHILA; human; Immunity; Immunity; ACTIN; cell migration; WAVE; Cell Shape; Cell Shape; Cell Shape; cell motility; Wiskott Aldrich syndrome protein; Arp2/3; Lamellipodia; CK2; casein kinase Ialpha; casein kinase Ialpha; CK1α; Ubiquitin-dependent protein degradation; Wiskott-Aldrich Syndrome Protein Family}, year = {2021}, eissn = {1477-9137} } @article{MTMT:32913578, title = {Morphometry of cellular behavior of coelomocytes from starfish Asterias amurensis}, url = {https://m2.mtmt.hu/api/publication/32913578}, author = {Karetin, Y.A.}, doi = {10.7717/peerj.12514}, journal-iso = {PEERJ}, journal = {PEERJ}, volume = {9}, unique-id = {32913578}, issn = {2167-8359}, abstract = {A comprehensive statistical analysis using a wide range of linear and non-linear morphological parameters enabled identification of the main stages in the in vitro dynamics of cell behavior of immune cells of the marine invertebrate Asterias amurensis (Echinodermata, Asteroidea). Three stages may be distinguished in the cell behavior, which are characterized by the differences in complexity of the cell boundary microsculpture as well as by the size and asymmetry of the cell and convex hull of the cell. The first stage (5 min after placing cells onto a substrate) is characterized by more complex cell morphology and an increase in the process number and spreading area. The second stage (15 min) is characterized by simplification of cell morphology, retraction of some processes, and rounding of cells upon continued cell spreading. At the third stage (60 min), new large processes with rounded contours emerge due to partial retraction of the flattened cell surface. Each stage is characterized by statistically significant differences in several linear and nonlinear parameters of the external morphology for all cell types. Copyright © 2021 Karetin}, keywords = {CLASSIFICATION; ARTICLE; human; controlled study; nonhuman; morphometry; morphometry; in vitro study; immunocompetent cell; cell surface; cell spreading; FRACTAL ANALYSIS; FRACTAL ANALYSIS; cell function; Coelomocytes; Marine invertebrate; Asterias amurensis; Asterias amurensis}, year = {2021}, eissn = {2167-8359} } @article{MTMT:32317577, title = {A parasitoid wasp of Drosophila employs preemptive and reactive strategies to deplete its host's blood cells}, url = {https://m2.mtmt.hu/api/publication/32317577}, author = {Ramroop, Johnny R. and Heavner, Mary Ellen and Razzak, Zubaidul H. and Govind, Shubha}, doi = {10.1371/journal.ppat.1009615}, journal-iso = {PLOS PATHOG}, journal = {PLOS PATHOGENS}, volume = {17}, unique-id = {32317577}, issn = {1553-7366}, abstract = {The wasps Leptopilina heterotoma parasitize and ingest their Drosophila hosts. They produce extracellular vesicles (EVs) in the venom that are packed with proteins, some of which perform immune suppressive functions. EV interactions with blood cells of host larvae are linked to hematopoietic depletion, immune suppression, and parasite success. But how EVs disperse within the host, enter and kill hematopoietic cells are not well understood. Using an antibody marker for L. heterotoma EVs, we show that these parasite-derived structures are readily distributed within the hosts' hemolymphatic system. EVs converge around the tightly clustered cells of the posterior signaling center (PSC) of the larval lymph gland, a small hematopoietic organ in Drosophila. The PSC serves as a source of developmental signals in naive animals. In wasp-infected animals, the PSC directs the differentiation of lymph gland progenitors into lamellocytes. These lamellocytes are needed to encapsulate the wasp egg and block parasite development. We found that L. heterotoma infection disassembles the PSC and PSC cells disperse into the disintegrating lymph gland lobes. Genetically manipulated PSC-less lymph glands remain non-responsive and largely intact in the face of L. heterotoma infection. We also show that the larval lymph gland progenitors use the endocytic machinery to internalize EVs. Once inside, L. heterotoma EVs damage the Rab7- and LAMP-positive late endocytic and phagolysosomal compartments. Rab5 maintains hematopoietic and immune quiescence as Rab5 knockdown results in hematopoietic over-proliferation and ectopic lamellocyte differentiation. Thus, both aspects of anti-parasite immunity, i.e., (a) phagocytosis of the wasp's immune-suppressive EVs, and (b) progenitor differentiation for wasp egg encapsulation reside in the lymph gland. These results help explain why the lymph gland is specifically and precisely targeted for destruction. The parasite's simultaneous and multipronged approach to block cellular immunity not only eliminates blood cells, but also tactically blocks the genetic programming needed for supplementary hematopoietic differentiation necessary for host success. In addition to its known functions in hematopoiesis, our results highlight a previously unrecognized phagocytic role of the lymph gland in cellular immunity. EV-mediated virulence strategies described for L. heterotoma are likely to be shared by other parasitoid wasps; their understanding can improve the design and development of novel therapeutics and biopesticides as well as help protect biodiversity.Author summary Parasitoid wasps serve as biological control agents of agricultural insect pests and are worthy of study. Many parasitic wasps develop inside their hosts to emerge as free-living adults. To overcome the resistance of their hosts, parasitic wasps use varied and ingenious strategies such as mimicry, evasion, bioactive venom, virus-like particles, viruses, and extracellular vesicles (EVs). We describe the effects of a unique class of EVs containing virulence proteins and produced in the venom of wasps that parasitize fruit flies of Drosophila species. EVs from Leptopilina heterotoma are widely distributed throughout the Drosophila hosts' circulatory system after infection. They enter and kill macrophages by destroying the very same subcellular machinery that facilitates their uptake. An important protein in this process, Rab5, is needed to maintain the identity of the macrophage; when Rab5 function is reduced, macrophages turn into a different cell type called lamellocytes. Activities in the EVs can eliminate lamellocytes as well. EVs also interfere with the hosts' genetic program that promotes lamellocyte differentiation needed to block parasite development. Thus, wasps combine specific preemptive and reactive strategies to deplete their hosts of the very cells that would otherwise sequester and kill them. These findings have applied value in agricultural pest control and medical therapeutics.}, year = {2021}, eissn = {1553-7374} } @article{MTMT:32361877, title = {Methotrexate negatively acts on inflammatory responses triggered in Drosophila larva with hyperactive JAK/STAT pathway}, url = {https://m2.mtmt.hu/api/publication/32361877}, author = {Yadav, Ravi Kant and Gautam, Dushyant Kumar and Muj, Chukhu and Balija, Madhu Babu Gajula and Paddibhatla, Indira}, doi = {10.1016/j.dci.2021.104161}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {123}, unique-id = {32361877}, issn = {0145-305X}, abstract = {Drosophila is a valuable paradigm for studying tumorigenesis and cancer. Mutations causing hematopoietic aberrations and melanotic-blood-tumors found in Drosophila mutants are vastly studied. Clear understanding about the blood cells, signaling pathways and the tissues affected during hematopoietic tumor formation provide an opportunity to delineate the effects of cancer therapeutics. Using this simple hematopoietic archetype, we elucidated the effects of the anti-cancer drug, Methotrexate (MTX) on immune responses in two scenarios i.e. against wasp infection and in hematopoietic mutant, hopTum-l. Through this in vivo study we show that MTX impedes the immune responses against wasp infection including the encapsulation response. We further observed that MTX reduces the tumor penetrance in gain-of-function mutants of JAK/STAT pathway, hopTum-l. MTX is antiinflammatory as it hinders not only the immune responses of acute inflammation as observed after wasp infestation, but also chronic inflammatory responses associated with constitutively activated JAK/STAT pathway mutant (hopTum-l) carrying blood tumors.}, keywords = {Inflammation; encapsulation; Hematopoiesis; lamellocytes; MTX; Blood tumor}, year = {2021}, eissn = {1879-0089} } @article{MTMT:31468414, title = {The Leukemic Fly: Promises and Challenges}, url = {https://m2.mtmt.hu/api/publication/31468414}, author = {Al Outa, Amani and Abubaker, Dana and Madi, Joelle and Nasr, Rihab and Shirinian, Margret}, doi = {10.3390/cells9071737}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {9}, unique-id = {31468414}, abstract = {Leukemia involves different types of blood cancers, which lead to significant mortality and morbidity. Murine models of leukemia have been instrumental in understanding the biology of the disease and identifying therapeutics. However, such models are time consuming and expensive in high throughput genetic and drug screening.Drosophilamelanogasterhas emerged as an invaluable in vivo model for studying different diseases, including cancer. Fruit flies possess several hematopoietic processes and compartments that are in close resemblance to their mammalian counterparts. A number of studies succeeded in characterizing the fly's response upon the expression of human leukemogenic proteins in hematopoietic and non-hematopoietic tissues. Moreover, some of these studies showed that these models are amenable to genetic screening. However, none were reported to be tested for drug screening. In this review, we describe theDrosophilahematopoietic system, briefly focusing on leukemic diseases in which fruit flies have been used. We discuss myeloid and lymphoid leukemia fruit fly models and we further highlight their roles for future therapeutic screening. In conclusion, fruit fly leukemia models constitute an interesting area which could speed up the process of integrating new therapeutics when complemented with mammalian models.}, keywords = {LEUKEMIA; Drosophila melanogaster; drug screening; Fruit fly; Blood cancer}, year = {2020}, eissn = {2073-4409}, orcid-numbers = {Nasr, Rihab/0000-0003-1166-4999} } @article{MTMT:32006196, title = {Transiently “Undead” Enterocytes Mediate Homeostatic Tissue Turnover in the Adult Drosophila Midgut}, url = {https://m2.mtmt.hu/api/publication/32006196}, author = {Amcheslavsky, A. and Lindblad, J.L. and Bergmann, A.}, doi = {10.1016/j.celrep.2020.108408}, journal-iso = {CELL REP}, journal = {CELL REPORTS}, volume = {33}, unique-id = {32006196}, issn = {2211-1247}, abstract = {We reveal surprising similarities between homeostatic cell turnover in adult Drosophila midguts and “undead” apoptosis-induced compensatory proliferation (AiP) in imaginal discs. During undead AiP, immortalized cells signal for AiP, allowing its analysis. Critical for undead AiP is the Myo1D-dependent localization of the initiator caspase Dronc to the plasma membrane. Here, we show that Myo1D functions in mature enterocytes (ECs) to control mitotic activity of intestinal stem cells (ISCs). In Myo1D mutant midguts, many signaling events involved in AiP (ROS generation, hemocyte recruitment, and JNK signaling) are affected. Importantly, similar to AiP, Myo1D is required for membrane localization of Dronc in ECs. We propose that ECs destined to die transiently enter an undead-like state through Myo1D-dependent membrane localization of Dronc, which enables them to generate signals for ISC activity and their replacement. The concept of transiently “undead” cells may be relevant for other stem cell models in flies and mammals. © 2020 The Authors Amcheslavsky et al. reveal a mechanism according to which apoptotic cells maintain survival transiently by entering an “undead”-like state through membrane localization of Dronc in a Myo1D-dependent manner. This transient “undead”-like state enables apoptotic cells for a short time to generate signals for mitotic activity of stem cells. © 2020 The Authors}, keywords = {Adult; Female; APOPTOSIS; PHENOTYPE; ARTICLE; signal transduction; Cell Survival; priority journal; controlled study; Cell Membrane; nonhuman; animal tissue; animal experiment; animal cell; cell proliferation; enzyme activity; cellular distribution; Mitosis; Drosophila melanogaster; Drosophila melanogaster; Homeostasis; PROTEIN FUNCTION; unclassified drug; cell migration; blood cell; reactive oxygen metabolite; epidermal growth factor receptor; JNK; stress activated protein kinase; cell metabolism; MYOSIN; cell activity; caspase; STAT protein; Caspase 9; intestine cell; mutant protein; Hemocyte; Midgut; Duox; JAK-STAT signaling; tissue metabolism; enterocyte; intestinal stem cell; apoptosis-induced proliferation; Dronc; Myo1D; posterior midgut; undead state; Dronc protein; myosin 1D; apoptosis induced compensatory proliferation}, year = {2020}, eissn = {2211-1247} } @article{MTMT:31686585, title = {Amalgam regulates the receptor tyrosine kinase pathway through Sprouty in glial cell development in the Drosophila larval brain}, url = {https://m2.mtmt.hu/api/publication/31686585}, author = {Ariss, Majd M. and Terry, Alexander R. and Islam, Abul B. M. M. K. and Hay, Nissim and Frolov, Maxim V}, doi = {10.1242/jcs.250837}, journal-iso = {J CELL SCI}, journal = {JOURNAL OF CELL SCIENCE}, volume = {133}, unique-id = {31686585}, issn = {0021-9533}, abstract = {The receptor tyrosine kinase (RTK) pathway plays an essential role in development and disease by controlling cell proliferation and differentiation. Here, we profile the Drosophila larval brain by single-cell RNA-sequencing and identify Amalgam (Ama), which encodes a cell adhesion protein of the immunoglobulin IgLON family, as regulating the RTK pathway activity during glial cell development. Depletion of Ama reduces cell proliferation, affects glial cell type composition and disrupts the blood-brain barrier (BBB), which leads to hemocyte infiltration and neuronal death. We show that Ama depletion lowers RTK activity by upregulating Sprouty (Sty), a negative regulator of the RTK pathway. Knockdown of Ama blocks oncogenic RTK signaling activation in the Drosophila glioma model and halts malignant transformation. Finally, knockdown of a human ortholog of Ama, LSAMP, results in upregulation of SPROUTY2 in glioblastoma cell lines, suggesting that the relationship between Ama and Sty is conserved.}, keywords = {DROSOPHILA; Blood-Brain Barrier; RECEPTOR TYROSINE KINASE; Single-Cell RNA-Sequencing; Lsamp; Sprouty}, year = {2020}, eissn = {1477-9137}, orcid-numbers = {Hay, Nissim/0000-0002-6245-3000; Frolov, Maxim V/0000-0003-3953-3739} } @article{MTMT:31469240, title = {Context-specific functions of Notch in Drosophila blood cell progenitors}, url = {https://m2.mtmt.hu/api/publication/31469240}, author = {Blanco-Obregon, D. and Katz, M. J. and Durrieu, L. and Gandara, L. and Wappner, P.}, doi = {10.1016/j.ydbio.2020.03.018}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {462}, unique-id = {31469240}, issn = {0012-1606}, abstract = {Drosophila Larval hematopoiesis takes place at the lymph gland, where myeloid-like progenitors differentiate into Plasmatocytes and Crystal Cells, under regulation of conserved signaling pathways. It has been established that the Notch pathway plays a specific role in Crystal Cell differentiation and maintenance. In mammalian hematopoiesis, the Notch pathway has been proposed to fulfill broader functions, including Hematopoietic Stem Cell maintenance and cell fate decision in progenitors. In this work we describe different roles that Notch plays in the lymph gland. We show that Notch, activated by its ligand Serrate, expressed at the Posterior Signaling Center, is required to restrain Core Progenitor differentiation. We define a novel population of blood cell progenitors that we name Distal Progenitors, where Notch, activated by Serrate expressed in Lineage Specifying Cells at the Medullary Zone/Cortical Zone boundary, regulates a binary decision between Plasmatocyte and Crystal Cell fates. Thus, Notch plays context-specific functions in different blood cell progenitor populations of the Drosophila lymph gland.}, keywords = {Notch signaling; lymph gland; Drosophila hematopoiesis; Blood cell progenitors}, year = {2020}, eissn = {1095-564X}, pages = {101-115} } @article{MTMT:31868487, title = {Single-cell transcriptome maps of myeloid blood cell lineages in Drosophila}, url = {https://m2.mtmt.hu/api/publication/31868487}, author = {Cho, B. and Yoon, S.-H. and Lee, D. and Koranteng, F. and Tattikota, S.G. and Cha, N. and Shin, M. and Do, H. and Hu, Y. and Oh, S.Y. and Lee, D. and Vipin, Menon A. and Moon, S.J. and Perrimon, N. and Nam, J.-W. and Shim, J.}, doi = {10.1038/s41467-020-18135-y}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {11}, unique-id = {31868487}, issn = {2041-1723}, abstract = {The Drosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and mature hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis and immunity. Three types of mature hemocytes have been characterized in the lymph gland: plasmatocytes, lamellocytes, and crystal cells, which are analogous to vertebrate myeloid cells, yet molecular underpinnings of the lymph gland hemocytes have been less investigated. Here, we use single-cell RNA sequencing to comprehensively analyze heterogeneity of developing hemocytes in the lymph gland, and discover previously undescribed hemocyte types including adipohemocytes, stem-like prohemocytes, and intermediate prohemocytes. Additionally, we identify the developmental trajectory of hemocytes during normal development as well as the emergence of the lamellocyte lineage following active cellular immunity caused by wasp infestation. Finally, we establish similarities and differences between embryonically derived- and larval lymph gland hemocytes. Altogether, our study provides detailed insights into the hemocyte development and cellular immune responses at single-cell resolution. © 2020, The Author(s).}, keywords = {Animals; metabolism; BLOOD; GENETICS; ARTICLE; RNA; DROSOPHILA; HEMOCYTES; animal; MAP; Cell Differentiation; Cell Differentiation; physiology; Cytology; nonhuman; Host-Parasite Interactions; Immunity; host parasite interaction; pathogenicity; pathology; parasitology; Vertebrata; immune system; Animals, Genetically Modified; Drosophila melanogaster; Drosophila melanogaster; Gene Expression Profiling; Gene Expression Profiling; cellular immunity; immune response; immune response; blood cell; blood cell; transcriptomics; lymphoid tissue; lymphoid tissue; transgenic animal; Cell Lineage; Cell Lineage; Transcriptome; Transcriptome; Transcriptome; lymph node; Hematopoiesis; Hematopoiesis; detection method; Wasps; myeloid progenitor cell; WASP; WASP; Single-Cell Analysis; single cell analysis; RNA-Seq; cells by body anatomy; cell component; single cell RNA seq; Ectoparasitosis; Ectoparasitic Infestations}, year = {2020}, eissn = {2041-1723} } @article{MTMT:30819399, title = {Cellular Immune Response Involving Multinucleated Giant Hemocytes with Two-Step Genome Amplification in the Drosophilid Zaprionus indianus}, url = {https://m2.mtmt.hu/api/publication/30819399}, author = {Cinege, Gyöngyi Ilona and Lerner, Zita and Magyar, Lilla Brigitta and Soós, Bálint and Tóth, Renáta and Kristó, Ildikó and Vilmos, Péter and Juhász, Gábor and Kovács, Attila Lajos and Hegedűs, Zoltán and Sensen, Christoph W. and Kurucz, Judit Éva and Andó, István}, doi = {10.1159/000502646}, journal-iso = {J INNATE IMMUN}, journal = {JOURNAL OF INNATE IMMUNITY}, volume = {12}, unique-id = {30819399}, issn = {1662-811X}, year = {2020}, eissn = {1662-8128}, pages = {257-272}, orcid-numbers = {Juhász, Gábor/0000-0001-8548-8874; Andó, István/0000-0002-4648-9396} } @article{MTMT:31469413, title = {The PAX-SIX-EYA-DACH network modulates GATA-FOG function in fly hematopoiesis and human erythropoiesis}, url = {https://m2.mtmt.hu/api/publication/31469413}, author = {Creed, T. Michael and Baldeosingh, Rajkumar and Eberly, Christian L. and Schlee, Caroline S. and Kim, MinJung and Cutler, Jevon A. and Pandey, Akhilesh and Civin, Curt I and Fossett, Nancy G. and Kingsbury, Tami J.}, doi = {10.1242/dev.177022}, journal-iso = {DEVELOPMENT}, journal = {DEVELOPMENT}, volume = {147}, unique-id = {31469413}, issn = {0950-1991}, abstract = {The GATA and PAX-SIX-EYA-DACH transcriptional networks (PSEDNs) are essential for proper development across taxa. Here, we demonstrate novel PSEDN roles in vivo in Drosophila hematopoiesis and in human erythropoiesis in vitro. Using Drosophila genetics, we show that PSEDN members function with GATA to block lamellocyte differentiation and maintain the prohemocyte pool. Overexpression of human SIX1 stimulated erythroid differentiation of human erythroleukemia TF1 cells and primary hematopoietic stem-progenitor cells. Conversely, SIX1 knockout impaired erythropoiesis in both cell types. SIX1 stimulation of erythropoiesis required GATA1, as SIX1 overexpression failed to drive erythroid phenotypes and gene expression patterns in GATA1 knockout cells. SIX1 can associate with GATA1 and stimulate GATA1-mediated gene transcription, suggesting that SIX1-GATA1 physical interactions contribute to the observed functional interactions. In addition, both fly and human SIX proteins regulated GATA protein levels. Collectively, our findings demonstrate that SIX proteins enhance GATA function at multiple levels, and reveal evolutionarily conserved cooperation between the GATA and PSEDN networks that may regulate developmental processes beyond hematopoiesis.}, keywords = {Hematopoiesis; GATA; six1; SIX2; Retinal determination gene network; PAX-SIX-EYA-DACH network}, year = {2020}, eissn = {1477-9129} } @article{MTMT:31686151, title = {Eater cooperates with Multiplexin to drive the formation of hematopoietic compartments}, url = {https://m2.mtmt.hu/api/publication/31686151}, author = {Csordás, Gábor and Grawe, Ferdinand and Uhlirova, Mirka}, doi = {10.7554/eLife.57297}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {9}, unique-id = {31686151}, issn = {2050-084X}, abstract = {Blood development in multicellular organisms relies on specific tissue microenvironments that nurture hematopoietic precursors and promote their self-renewal, proliferation, and differentiation. The mechanisms driving blood cell homing and their interactions with hematopoietic microenvironments remain poorly understood. Here, we use the Drosophila melanogaster model to reveal a pivotal role for basement membrane composition in the formation of hematopoietic compartments. We demonstrate that by modulating extracellular matrix components, the fly blood cells known as hemocytes can be relocated to tissue surfaces where they function similarly to their natural hematopoietic environment. We establish that the Collagen XV/XVIII ortholog Multiplexin in the tissue-basement membranes and the phagocytosis receptor Eater on the hemocytes physically interact and are necessary and sufficient to induce immune cell-tissue association. These results highlight the cooperation of Multiplexin and Eater as an integral part of a homing mechanism that specifies and maintains hematopoietic sites in Drosophila}, year = {2020}, eissn = {2050-084X}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839} } @article{MTMT:31469410, title = {Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue}, url = {https://m2.mtmt.hu/api/publication/31469410}, author = {Diwanji, Neha and Bergmann, Andreas}, doi = {10.1038/s41467-020-17399-8}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {11}, unique-id = {31469410}, issn = {2041-1723}, abstract = {Macrophages are a major immune cell type infiltrating tumors and promoting tumor growth and metastasis. To elucidate the mechanism of macrophage recruitment, we utilize an overgrowth tumor model ("undead" model) in larval Drosophila imaginal discs that are attached by numerous macrophages. Here we report that changes to the microenvironment of the overgrown tissue are important for recruiting macrophages. First, we describe a correlation between generation of reactive oxygen species (ROS) and damage of the basement membrane (BM) in all neoplastic, but not hyperplastic, models examined. ROS and the stress kinase JNK mediate the accumulation of matrix metalloproteinase 2 (Mmp2), damaging the BM, which recruits macrophages to the tissue. We propose a model where macrophage recruitment to and activation at overgrowing tissue is a multi-step process requiring ROS- and JNK-mediated Mmp2 upregulation and BM damage. These findings have implications for understanding the role of the tumor microenvironment for macrophage activation. The molecular mechanisms regulating macrophage recruitment to tumors are unclear. Here, the authors use a Drosophila overgrowth model to show how damaged basement membranes recruit macrophages to undead tissue, via an interdependent effect of reactive oxygen species and matrix metalloproteinase 2.}, year = {2020}, eissn = {2041-1723}, orcid-numbers = {Diwanji, Neha/0000-0001-9828-5793; Bergmann, Andreas/0000-0002-9134-871X} } @article{MTMT:31469242, title = {Single-cell RNA sequencing identifies novel cell types in Drosophila blood}, url = {https://m2.mtmt.hu/api/publication/31469242}, author = {Fu, Yulong and Huang, Xiaohu and Zhang, Peng and van de Leemput, Joyce and Han, Zhe}, doi = {10.1016/j.jgg.2020.02.004}, journal-iso = {J GENET GENOMICS}, journal = {JOURNAL OF GENETICS AND GENOMICS}, volume = {47}, unique-id = {31469242}, issn = {1673-8527}, abstract = {Drosophila has been extensively used to model the human blood-immune system, as both systems share many developmental and immune response mechanisms. However, while many human blood cell types have been identified, only three were found in flies: plasmatocytes, crystal cells and lamellocytes. To better understand the complexity of fly blood system, we used single-cell RNA sequencing technology to generate comprehensive gene expression profiles for Drosophila circulating blood cells. In addition to the known cell types, we identified two new Drosophila blood cell types: thanacytes and primocytes. Thanacytes, which express many stimulus response genes, are involved in distinct responses to different types of bacteria. Primocytes, which express cell fate commitment and signaling genes, appear to be involved in keeping stem cells in the circulating blood. Furthermore, our data revealed four novel plasmatocyte subtypes (Ppn(+), CAH7(+), Lsp(+) and reservoir plasmatocytes), each with unique molecular identities and distinct predicted functions. We also identified cross-species markers from Drosophila hemocytes to human blood cells. Our analysis unveiled a more complex Drosophila blood system and broadened the scope of using Drosophila to model human blood system in development and disease. Copyright (C) 2020, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.}, keywords = {BLOOD; DROSOPHILA; Plasmatocyte; Single-cell RNA-seq; Thanacyte; Primocyte}, year = {2020}, eissn = {1873-5533}, pages = {175-186}, orcid-numbers = {Zhang, Peng/0000-0002-6218-1885; Han, Zhe/0000-0002-5177-7798} } @article{MTMT:31302837, title = {Identification of reference markers for characterizing honey bee (Apis mellifera) hemocyte classes}, url = {https://m2.mtmt.hu/api/publication/31302837}, author = {Gábor, Erika and Cinege, Gyöngyi Ilona and Csordás, Gábor and Rusvai, Miklós and Honti, Viktor and Kolics, Balázs and Török, Tibor and Williams, Michael J and Kurucz, Judit Éva and Andó, István}, doi = {10.1016/j.dci.2020.103701}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {109}, unique-id = {31302837}, issn = {0145-305X}, abstract = {Cell mediated immunity of the honey bee (Apis mellifera) involves the activity of several hemocyte populations, currently defined by morphological features and lectin binding characteristics. The objective of the present study was to identify molecular markers capable of characterizing subsets of honey bee hemocytes. We developed and employed monoclonal antibodies with restricted reactions to functionally distinct hemocyte subpopulations. Melanizing cells, known as oenocytoids, were defined by an antibody to prophenoloxidase, aggregating cells were identified by the expression of Hemolectin, and phagocytic cells were identified by a marker expressed on granulocytes. We anticipate that this combination of antibodies not only allows for the detection of functionally distinct hemocyte subtypes, but will help to further the exploration of hematopoietic compartments, as well as reveal details of the honey bee cellular immune defense against parasites and microbes.}, keywords = {Immunity; monoclonal antibody; Hemocyte; Apis mellifera; Honey bee; insect immunity}, year = {2020}, eissn = {1879-0089}, pages = {103701-103706}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Török, Tibor/0000-0002-2128-1126; Andó, István/0000-0002-4648-9396} } @article{MTMT:31686512, title = {Development of two continuous hemocyte cell sublines in the Asian corn borerOstrinia furnacalisand the identification of molecular markers for hemocytes}, url = {https://m2.mtmt.hu/api/publication/31686512}, author = {Hu, Jian and Du, Yan and Meng, Meng and Dong, Yipei and Peng, Jiewen}, doi = {10.1111/1744-7917.12854}, journal-iso = {INSECT SCI}, journal = {INSECT SCIENCE}, unique-id = {31686512}, issn = {1672-9609}, abstract = {Granulocytes and plasmatocytes play important roles in clearing foreign objects in insects, but it is difficult to distinguish between them in immune reactions. Based on the hemocyte cell line SYSU-OfHe-C established at our lab, two cell sublines, SYSU-OfHe-C Granulocyte (Gr cells) and SYSU-OfHe-C Plasmatocyte (Pl cells), which possess the morphological characteristics of granulocytes and plasmatocytes, respectively, were established. Gr and Pl cells showed different behaviors in immune reactions, such as spreading, phagocytosis and encapsulation. Pl cells were easier to spread, but Gr cells tended to undergo aggregation, indicating that they may take different strategies to clear foreign objects. These results also suggested that granulocytes and plasmatocytes may express some different proteins. By comparing the gene expression in cells from the two sublines, 1662 differentially expressed genes were identified, and 13 out of 30 transmembrane proteins highly expressed in Pl cells (six) or Gr cells (seven) were further screened and confirmed by reverse-transcription polymerase chain reaction (PCR). Finally, three transmembrane genes specifically expressed in Pl cells and two transmembrane genes specifically expressed in Gr cells were screened out based on their expressions in immune reactions by quantitative PCR analysis. These genes may potentially be used as molecular markers to distinguish between granulocytes and plasmatocytes inOstrinia furnacalis, and further to clarify the functions of immune hemocytes in cellular immune reaction such as encapsulation and so on.}, keywords = {INSECT; Molecular marker; granulocyte; Hemocyte; Plasmatocyte; cell sublines}, year = {2020}, eissn = {1744-7917} } @article{MTMT:32006195, title = {Adapting drosophila melanogaster cell lines to serum-free culture conditions}, url = {https://m2.mtmt.hu/api/publication/32006195}, author = {Luhur, A. and Mariyappa, D. and Klueg, K.M. and Buddika, K. and Tennessen, J.M. and Zelhof, A.C.}, doi = {10.1534/g3.120.401769}, journal-iso = {G3-GENES GENOM GENET}, journal = {G3-GENES GENOMES GENETICS}, volume = {10}, unique-id = {32006195}, issn = {2160-1836}, abstract = {Successful Drosophila cell culture relies on media containing xenogenic components such as fetal bovine serum to support continuous cell proliferation. Here, we report a serum-free culture condition that supports the growth and proliferation of Drosophila S2R+ and Kc167 cell lines. Importantly, the gradual adaptation of S2R+ and Kc167 cells to a media lacking serum was supported by supplementing the media with adult Drosophila soluble extract, commonly known as fly extract. The utility of these adapted cells lines is largely unchanged. The adapted cells exhibited robust proliferative capacity and a transfection efficiency that was comparable to control cells cultured in serum-containing media. Transcriptomic data indicated that the S2R+ cells cultured with fly extract retain their hemocyte-specific transcriptome profile, and there were no global changes in the transcriptional output of cell signaling pathways. Our metabolome studies indicate that there were very limited metabolic changes. In fact, the cells were likely experiencing less oxidative stress when cultured in the serum-free media supplemented with fly extract. Overall, the Drosophila cell culture conditions reported here consequently provide researchers with an alternative and physiologically relevant resource to address cell biological research questions. Copyright © 2020 Luhur et al.}, keywords = {Adult; Female; Male; CELLS; ARTICLE; signal transduction; DROSOPHILA; ADAPTATION; controlled study; nonhuman; animal cell; cell proliferation; Drosophila melanogaster; Cell Line; cell culture; blood cell; transcriptomics; genetic transfection; Transcriptome; Transcriptome; Metabolome; Metabolome; Global change; insect cell; serum-free; Oxidative stress; Fly extract; S2R+; kc167 cell line; s2r cell line}, year = {2020}, eissn = {2160-1836}, pages = {4541-4551} } @article{MTMT:31469409, title = {The Posterior Signaling Center Is an Important Microenvironment for Homeostasis of the Drosophila Lymph Gland}, url = {https://m2.mtmt.hu/api/publication/31469409}, author = {Luo, Fangzhou and Yu, Shichao and Jin, Li Hua}, doi = {10.3389/fcell.2020.00382}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {8}, unique-id = {31469409}, issn = {2296-634X}, abstract = {Hematopoiesis is a necessary process for development and immune defense in Drosophila from the embryonic period to adulthood. There are two main stages in this process: the first stage occurs in the head mesoderm during the embryonic stage, and the second occurs in a specialized hematopoietic organ along the dorsal vessel, the lymph gland, during the larval stage. The lymph gland consists of paired lobes, each of which has distinct regions: the cortical zone (CZ), which contains mature hemocytes; the medullary zone (MZ), which contains hematopoietic progenitors; and the posterior signaling center (PSC), which specifically expresses the early B-cell factor (EBF) transcription factor Collier (Col) and the HOX factor Antennapedia (Antp) to form a microenvironment similar to that of the mammalian bone marrow hematopoietic stem cell niche. The PSC plays a key role in regulating hematopoietic progenitor differentiation. Moreover, the PSC contributes to the cellular immune response to wasp parasitism triggered by elevated ROS levels. Two recent studies have revealed that hematopoietic progenitor maintenance is directly regulated by Col expressed in the MZ and is independent of the PSC, challenging the traditional model. In this review, we summarize the regulatory networks of PSC cell proliferation, the controversy regarding PSC-mediated regulation of hematopoietic progenitor differentiation, and the wasp egg infection response. In addition, we discuss why the PSC is an ideal model for investigating mammalian hematopoietic stem cell niches and leukemia.}, keywords = {DIFFERENTIATION; LEUKEMIA; DROSOPHILA; immune response; Signaling network; lymph gland; posterior signaling center; hematopoietic stem cells niche}, year = {2020}, eissn = {2296-634X} } @article{MTMT:31467726, title = {Subpopulation of Macrophage-Like Plasmatocytes Attenuates Systemic Growth via JAK/STAT in the Drosophila Fat Body}, url = {https://m2.mtmt.hu/api/publication/31467726}, author = {Shin, Mingyu and Cha, Nuri and Koranteng, Ferdinand and Cho, Bumsik and Shim, Jiwon}, doi = {10.3389/fimmu.2020.00063}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {11}, unique-id = {31467726}, issn = {1664-3224}, abstract = {Drosophila hemocytes, like those of mammals, are given rise from two distinctive phases during both the embryonic and larval hematopoiesis. Embryonically derived hemocytes, mostly composed of macrophage-like plasmatocytes, are largely identified by genetic markers. However, the cellular diversity and distinct functions of possible subpopulations within plasmatocytes have not been explored in Drosophila larvae. Here, we show that larval plasmatocytes exhibit differential expressions of Hemolectin (Hml) and Peroxidasin (Pxn) during development. Moreover, removal of plasmatocytes by overexpressing pro-apoptotic genes, hid and reaper in Hml-positive plasmatocytes, feeding high sucrose diet, or wasp infestation results in increased circulating hemocytes that are Hml-negative. Interestingly these Hml-negative plasmatocytes retain Pxn expression, and animals expressing Hml-negative and Pxn-positive subtype largely attenuate growth and abrogate metabolism. Furthermore, elevated levels of a cytokine, unpaired 3, are detected when Hml-positive hemocytes are ablated, which in turn activates JAK/STAT activity in several tissues including the fat body. Finally, we observed that insulin signaling is inhibited in this background, which can be recovered by concurrent loss of upd3. Overall, this study highlights heterogeneity in Drosophila plasmatocytes and a functional plasticity of each subtype, which reaffirms extension of their role beyond immunity into metabolic regulation for cooperatively maintaining internal homeostatic balance.}, keywords = {Drosophila melanogaster; Peroxidasin; insulin signaling; plasmatocytes; JAK/STAT; upd3; Hemolectin}, year = {2020}, eissn = {1664-3224}, orcid-numbers = {Koranteng, Ferdinand/0000-0002-0545-2423; Shim, Jiwon/0000-0003-2409-1130} } @article{MTMT:31468416, title = {A single-cell survey of Drosophila blood}, url = {https://m2.mtmt.hu/api/publication/31468416}, author = {Tattikota, Sudhir Gopal and Cho, Bumsik and Liu, Yifang and Hu, Yanhui and Barrera, Victor and Steinbaugh, Michael J. and Yoon, Sang-Ho and Comjean, Aram and Li, Fangge and Dervis, Franz and Hung, Ruei-Jiun and Nam, Jin-Wu and Sui, Shannan Ho and Shim, Jiwon and Perrimon, Norbert}, doi = {10.7554/eLife.54818}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {9}, unique-id = {31468416}, issn = {2050-084X}, abstract = {Drosophila blood cells, called hemocytes, are classified into plasmatocytes, crystal cells, and lamellocytes based on the expression of a few marker genes and cell morphologies, which are inadequate to classify the complete hemocyte repertoire. Here, we used single-cell RNA sequencing (scRNA-seq) to map hemocytes across different inflammatory conditions in larvae. We resolved plasmatocytes into different states based on the expression of genes involved in cell cycle, antimicrobial response, and metabolism together with the identification of intermediate states. Further, we discovered rare subsets within crystal cells and lamellocytes that express fibroblast growth factor (FGF) ligand branchless and receptor breathless, respectively. We demonstrate that these FGF components are required for mediating effective immune responses against parasitoid wasp eggs, highlighting a novel role for FGF signaling in inter-hemocyte crosstalk. Our scRNA-seq analysis reveals the diversity of hemocytes and provides a rich resource of gene expression profiles for a systems-level understanding of their functions.}, year = {2020}, eissn = {2050-084X}, orcid-numbers = {Tattikota, Sudhir Gopal/0000-0003-0318-5533; Cho, Bumsik/0000-0003-1989-0624; Yoon, Sang-Ho/0000-0003-2611-5554} } @article{MTMT:31045614, title = {The conserved metalloprotease invadolysin is present in invertebrate haemolymph and vertebrate blood}, url = {https://m2.mtmt.hu/api/publication/31045614}, author = {Abhinav, Kanishk and Feng, Linda and Morrison, Emma and Jung, Yunshin and Dear, James and Takahashi, Satoru and Heck, Margarete M. S.}, doi = {10.1242/bio.044073}, journal-iso = {BIOL OPEN}, journal = {BIOLOGY OPEN}, volume = {8}, unique-id = {31045614}, issn = {2046-6390}, abstract = {We identified invadolysin, a novel essential metalloprotease, for functions in chromosome structure, cell proliferation and migration. Invadolysin also plays an important metabolic role in insulin signalling and is the only protease known to localise to lipid droplets, the main lipid storage organelle in the cell. In silico examination of the protein sequence of invadolysin predicts not only protease and lipase catalytic motifs, but also post-translational modifications and the secretion of invadolysin. Here we show that the protease motif of invadolysin is important for its role in lipid accumulation, but not in glycogen accumulation. The lipase motif does not appear to be functionally important for the accumulation of lipids or glycogen. Post-translational modifications likely contribute to modulating the level, localisation or activity of invadolysin. We identified a secreted form of invadolysin in the soluble fraction of invertebrate hemolymph (where we observe sexually dimorphic forms) and also vertebrate plasma, including in the extracellular vesicle fraction. Biochemical analysis for various post-translational modifications demonstrated that secreted invadolysin is both N- and O-glycosylated, but not apparently GPI-linked. The discovery of invadolysin in the extracellular milieu suggests a role for invadolysin in normal organismal physiology.}, keywords = {PLASMA; PROTEASE; Hemolymph; Metalloprotease; Invadolysin}, year = {2019}, eissn = {2046-6390} } @article{MTMT:30510237, title = {Drosophila as a Genetic Model for Hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/30510237}, author = {Banerjee, Utpal and Girard, Juliet R. and Goins, Lauren M. and Spratford, Carrie M.}, doi = {10.1534/genetics.118.300223}, journal-iso = {GENETICS}, journal = {GENETICS}, volume = {211}, unique-id = {30510237}, issn = {0016-6731}, abstract = {In this FlyBook chapter, we present a survey of the current literature on the development of the hematopoietic system in Drosophila. The Drosophila blood system consists entirely of cells that function in innate immunity, tissue integrity, wound healing, and various forms of stress response, and are therefore functionally similar to myeloid cells in mammals. The primary cell types are specialized for phagocytic, melanization, and encapsulation functions. As in mammalian systems, multiple sites of hematopoiesis are evident in Drosophila and the mechanisms involved in this process employ many of the same molecular strategies that exemplify blood development in humans. Drosophila blood progenitors respond to internal and external stress by coopting developmental pathways that involve both local and systemic signals. An important goal of these Drosophila studies is to develop the tools and mechanisms critical to further our understanding of human hematopoiesis during homeostasis and dysfunction.}, keywords = {DROSOPHILA; innate immunity; Hematopoiesis; stress response; Lamellocyte; Hemocyte; Plasmatocyte; lymph gland; FlyBook; crystal cell}, year = {2019}, eissn = {1943-2631}, pages = {367-417} } @article{MTMT:31072775, title = {Adult Drosophila Lack Hematopoiesis but Rely on a Blood Cell Reservoir at the Respiratory Epithelia to Relay Infection Signals to Surrounding Tissues}, url = {https://m2.mtmt.hu/api/publication/31072775}, author = {Bosch, Pablo Sanchez and Makhijani, Kalpana and Herboso, Leire and Gold, Katrina S. and Baginsky, Rowan and Woodcock, Katie J. and Alexander, Brandy and Kukar, Katelyn and Corcoran, Sean and Jacobs, Thea and Ouyang, Debra and Wong, Corinna and Ramond, Elodie J. V. and Rhiner, Christa and Moreno, Eduardo and Lemaitre, Bruno and Geissmann, Frederic and Bruckner, Katja}, doi = {10.1016/j.devcel.2019.10.017}, journal-iso = {DEV CELL}, journal = {DEVELOPMENTAL CELL}, volume = {51}, unique-id = {31072775}, issn = {1534-5807}, abstract = {The use of adult Drosophila melanogaster as a model for hematopoiesis or organismal immunity has been debated. Addressing this question, we identify an extensive reservoir of blood cells (hemocytes) at the respiratory epithelia (tracheal air sacs) of the thorax and head. Lineage tracing and functional analyses demonstrate that the majority of adult hemocytes are phagocytic macrophages (plasmatocytes) from the embryonic lineage that parallels vertebrate tissue macrophages. Surprisingly, we find no sign of adult hemocyte expansion. Instead, hemocytes play a role in relaying an innate immune response to the blood cell reservoir: through Mid signaling and the Jak/Stat pathway ligand Upd3, hemocytes act as sentinels of bacterial infection, inducing expression of the antimicrobial peptide Drosocin in respiratory epithelia and colocalizing fat body domains. Drosocin expression in turn promotes animal survival after infection. Our work identifies a multisignal relay of organismal humoral immunity, establishing adult Drosophila as model for inter-organ immunity.}, year = {2019}, eissn = {1878-1551}, pages = {787-+}, orcid-numbers = {Rhiner, Christa/0000-0001-7577-8042} } @article{MTMT:30907377, title = {Pericardin, a Drosophila collagen, facilitates accumulation of hemocytes at the heart}, url = {https://m2.mtmt.hu/api/publication/30907377}, author = {Cevik, Duygu and Acker, Meryl and Michalski, Camilla and Jacobs, J. Roger}, doi = {10.1016/j.ydbio.2019.06.006}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {454}, unique-id = {30907377}, issn = {0012-1606}, abstract = {Hematopoietic cell lineages support organismal needs by responding to positional and systemic signals that balance proliferative and differentiation events. Drosophila provides an excellent genetic model to dissect these signals, where the activity of cues in the hemolymph or substrate can be traced to determination and differentiation events of well characterized hemocyte types. Plasmatocytes in third instar larvae increase in number in response to infection and in anticipation of metamorphosis. Here we characterize hemocyte clustering, proliferation and transdifferentiation on the heart or dorsal vessel. Hemocytes accumulate on the inner foldings of the heart basement membrane, where they move with heart contraction, and are in proximity to the heart ostia and pericardial nephrocytes. The numbers of hemocytes vary, but increase transiently before pupariation, and decrease by 4 h before pupa formation. During their accumulation at the heart, plasmatocytes can proliferate and can transdifferentiate into crystal cells. Serrate expressing cells as well as lamellocyte-like, Atilla expressing ensheathing cells are associated with some, but not all hemocyte clusters. Hemocyte aggregation is enhanced by the presence of a heart specific Collagen, Pericardin, but not the associated pericardial cells. The varied and transient number of hemocytes in the pericardial compartment suggests that this is not a hematopoietic hub, but a niche supporting differentiation and rapid dispersal in response to systemic signals.}, keywords = {INFECTION; niche; extracellular matrix; Hematopoiesis; Lamellocyte; Plasmatocyte; dorsal vessel; klf15; Viking. lonely heart}, year = {2019}, eissn = {1095-564X}, pages = {52-65} } @article{MTMT:30907275, title = {Drosophila Cellular Immunity Against Parasitoid Wasps: A Complex and Time-Dependent Process}, url = {https://m2.mtmt.hu/api/publication/30907275}, author = {Kim-Jo, Chami and Gatti, Jean-Luc and Poirie, Marylene}, doi = {10.3389/fphys.2019.00603}, journal-iso = {FRONT PHYSIOL}, journal = {FRONTIERS IN PHYSIOLOGY}, volume = {10}, unique-id = {30907275}, abstract = {Host-parasitoid interactions are among the most studied interactions between invertebrates because of their fundamental interest - the evolution of original traits in parasitoids - and applied, parasitoids being widely used in biological control. Immunity, and in particular cellular immunity, is central in these interactions, the host encapsulation response being specific for large foreign bodies such as parasitoid eggs. Although already well studied in this species, recent data on Drosophila melanogaster have unquestionably improved knowledge of invertebrate cellular immunity. At the same time, the venomics of parasitoids has expanded, notably those of Drosophila. Here, we summarize and discuss these advances, with a focus on an emerging "time-dependent" view of interactions outcome at the intra- and interspecific level. We also present issues still in debate and prospects for study. Data on the Drosophila-parasitoid model paves the way to new concepts in insect immunity as well as parasitoid wasp strategies to overcome it.}, keywords = {VENOM; DROSOPHILA; Immunity; encapsulation; Hematopoiesis; Parasitoid wasp; Leptopilina}, year = {2019}, eissn = {1664-042X} } @article{MTMT:30510577, title = {A comparative global proteomic analysis of the hematopoietic lineages in the crustacean Pacifastacus leniusculus}, url = {https://m2.mtmt.hu/api/publication/30510577}, author = {Soderhall, Irene and Junkunlo, Kingkamon}, doi = {10.1016/j.dci.2018.11.016}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {92}, unique-id = {30510577}, issn = {0145-305X}, abstract = {In crustaceans as in other arthropods, the circulating hemocytes are vital for protecting the animal against attacking microorganisms. As many hemocytes are destroyed early during an infection, new hemocytes must fast get in place to prevent disperse of a pathogenic microbe, In order to understand the hematopoietic process in more detail we here report a complete proteomic analysis from purified cell types from the APC of the hematopoietic tissue, via the remaining parts of the HPT to the mature semigranular and granular hemocytes. Several possible cell type specific proteins are detected and new putative biomarkers within the crayfish hematopoietic lineage that can be used to increase the understanding of how the differentiation process is regulated is described.}, keywords = {innate immunity; Crustacea; invertebrate; biomarker; proteome; Hematopoiesis}, year = {2019}, eissn = {1879-0089}, pages = {170-178} } @article{MTMT:30510580, title = {The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis in Drosophila and Preserves the Glial Fate}, url = {https://m2.mtmt.hu/api/publication/30510580}, author = {Trebuchet, Guillaume and Cattenoz, pierre B. and Zsamboki, Janos and Mazaud, David and Siekhaus, Edaria E. and Fanto, Manolis and Giangrande, Angela}, doi = {10.1523/JNEUROSCI.1059-18.2018}, journal-iso = {J NEUROSCI}, journal = {JOURNAL OF NEUROSCIENCE}, volume = {39}, unique-id = {30510580}, issn = {0270-6474}, abstract = {Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system, whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside (hemocytes) the nervous system require the same transcription factor glial cells deficient/glial cells missing (Glide/Gcm) for their development. This raises the issue of how do glia specifically differentiate in the nervous system, and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and panglial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us to understand the bases of cell specification. Both sexes were analyzed.}, keywords = {DROSOPHILA; HEMOCYTES; Glia; GLIDE; Gcm; repo}, year = {2019}, eissn = {1529-2401}, pages = {238-255}, orcid-numbers = {Mazaud, David/0000-0003-3998-9330} } @article{MTMT:30585796, title = {Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/30585796}, author = {Varga, Gergely István and Csordás, Gábor and Cinege, Gyöngyi Ilona and Jankovics, Ferenc and Sinka, Rita and Kurucz, Judit Éva and Andó, István and Honti, Viktor}, doi = {10.3390/genes10030173}, journal-iso = {GENES-BASEL}, journal = {GENES}, volume = {10}, unique-id = {30585796}, issn = {2073-4425}, abstract = {Due to the evolutionary conservation of the regulation of hematopoiesis, Drosophila provides an excellent model organism to study blood cell differentiation and hematopoietic stem cell (HSC) maintenance. The larvae of Drosophila melanogaster respond to immune induction with the production of special effector blood cells, the lamellocytes, which encapsulate and subsequently kill the invader. Lamellocytes differentiate as a result of a concerted action of all three hematopoietic compartments of the larva: the lymph gland, the circulating hemocytes, and the sessile tissue. Within the lymph gland, the communication of the functional zones, the maintenance of HSC fate, and the differentiation of effector blood cells are regulated by a complex network of signaling pathways. Applying gene conversion, mutational analysis, and a candidate based genetic interaction screen, we investigated the role of Headcase (Hdc), the homolog of the tumor suppressor HECA in the hematopoiesis of Drosophila. We found that naive loss-of-function hdc mutant larvae produce lamellocytes, showing that Hdc has a repressive role in effector blood cell differentiation. We demonstrate that hdc genetically interacts with the Hedgehog and the Decapentaplegic pathways in the hematopoietic niche of the lymph gland. By adding further details to the model of blood cell fate regulation in the lymph gland of the larva, our findings contribute to the better understanding of HSC maintenance.}, keywords = {DIFFERENTIATION; DROSOPHILA; innate immunity; blood cell; niche; Hematopoiesis; Hemocyte}, year = {2019}, eissn = {2073-4425}, orcid-numbers = {Varga, Gergely István/0000-0001-9073-5788; Csordás, Gábor/0000-0001-6871-6839; Sinka, Rita/0000-0003-4040-4184; Andó, István/0000-0002-4648-9396} } @article{MTMT:27602734, title = {Plasma Membrane Localization of Apoptotic Caspases for Non-apoptotic Functions}, url = {https://m2.mtmt.hu/api/publication/27602734}, author = {Amcheslavsky, Alla and Wang, Shiuan and Fogarty, Caitlin E and Lindblad, Jillian L and Fan, Yun and Bergmann, Andreas}, doi = {10.1016/j.devcel.2018.04.020}, journal-iso = {DEV CELL}, journal = {DEVELOPMENTAL CELL}, volume = {45}, unique-id = {27602734}, issn = {1534-5807}, year = {2018}, eissn = {1878-1551}, pages = {450-+} } @article{MTMT:30510582, title = {Hedgehog signaling from the Posterior Signaling Center maintains U-shaped expression and a prohemocyte population in Drosophila}, url = {https://m2.mtmt.hu/api/publication/30510582}, author = {Baldeosingh, Rajkumar and Gao, Hongjuan and Wu, Xiaorong and Fossett, Nancy}, doi = {10.1016/j.ydbio.2018.06.020}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {441}, unique-id = {30510582}, issn = {0012-1606}, abstract = {Hematopoietic progenitor choice between multipotency and differentiation is tightly regulated by intrinsic factors and extrinsic signals from the surrounding microenvironment. The Drosophila melanogaster hematopoietic lymph gland has emerged as a powerful tool to investigate mechanisms that regulate hematopoietic progenitor choice in vivo. The lymph gland contains progenitor cells, which share key characteristics with mammalian hematopoietic progenitors such as quiescence, multipotency and niche dependence. The lymph gland is zonally arranged, with progenitors located in medullary zone, differentiating cells in the cortical zone, and the stem cell niche or Posterior Signaling Center (PSC) residing at the base of the medullary zone (MZ). This arrangement facilitates investigations into how signaling from the microenvironment controls progenitor choice. The Drosophila Friend of GATA transcriptional regulator, U-shaped, is a conserved hematopoietic regulator. To identify additional novel intrinsic and extrinsic regulators that interface with U-shaped to control hematopoiesis, we conducted an in vivo screen for factors that genetically interact with u-shaped. Smoothened, a downstream effector of Hedgehog signaling, was one of the factors identified in the screen. Here we report our studies that characterized the relationship between Smoothened and U-shaped. We showed that the PSC and Hedgehog signaling are required for U-shaped expression and that U-shaped is an important intrinsic progenitor regulator. These observations identify a potential link between the progenitor regulatory machinery and extrinsic signals from the PSC. Furthermore, we showed that both Hedgehog signaling and the PSC are required to maintain a subpopulation of progenitors. This led to a delineation of PSC-dependent versus PSC-independent progenitors and provided further evidence that the MZ progenitor population is heterogeneous. Overall, we have identified a connection between a conserved hematopoietic master regulator and a putative stem cell niche, which adds to our understanding of how signals from the microenvironment regulate progenitor multipotency.}, year = {2018}, eissn = {1095-564X}, pages = {132-145} } @article{MTMT:30425005, title = {Extraction of Hemocytes from Drosophila melanogaster Larvae for Microbial Infection and Analysis}, url = {https://m2.mtmt.hu/api/publication/30425005}, author = {Hiroyasu, Aoi and DeWitt, David C. and Goodman, Alan G.}, doi = {10.3791/57077}, journal-iso = {JOVE-J VIS EXP}, journal = {JOVE-JOURNAL OF VISUALIZED EXPERIMENTS}, unique-id = {30425005}, issn = {1940-087X}, abstract = {During the pathogenic infection of Drosophila melanogaster, hemocytes play an important role in the immune response throughout the infection. Thus, the goal of this protocol is to develop a method to visualize the pathogen invasion in a specific immune compartment of flies, namely hemocytes. Using the method presented here, up to 3 x 10(6) live hemocytes can be obtained from 200 Drosophila 3rd instar larvae in 30 min for ex vivo infection. Alternatively, hemocytes can be infected in vivo through injection of 3rd instar larvae followed by hemocyte extraction up to 24 h post-infection. These infected primary cells were fixed, stained, and imaged using confocal microscopy. Then, 3D representations were generated from the images to definitively show pathogen invasion. Additionally, high-quality RNA for qRT-PCR can be obtained for the detection of pathogen mRNA following infection, and sufficient protein can be extracted from these cells for Western blot analysis. Taken together, we present a method for definite reconciliation of pathogen invasion and confirmation of infection using bacterial and viral pathogen types and an efficient method for hemocyte extraction to obtain enough live hemocytes from Drosophila larvae for ex vivo and in vivo infection experiments.}, keywords = {confocal microscopy; Listeria monocytogenes; Coxiella burnetii; Issue 135; Immunology and Infection; Pathogen invasion; hemocyte extraction; Invertebrate iridescent virus-6; IIV6}, year = {2018}, eissn = {1940-087X} } @article{MTMT:27602732, title = {A high-sugar diet affects cellular and humoral immune responses in Drosophila}, url = {https://m2.mtmt.hu/api/publication/27602732}, author = {Yu, Shichao and Zhang, Gaoqun and Jin, Li Hua}, doi = {10.1016/j.yexcr.2018.04.032}, journal-iso = {EXP CELL RES}, journal = {EXPERIMENTAL CELL RESEARCH}, volume = {368}, unique-id = {27602732}, issn = {0014-4827}, year = {2018}, eissn = {1090-2422}, pages = {215-224} } @article{MTMT:27602733, title = {The Drosophila lymph gland is an ideal model for studying hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/27602733}, author = {Yu, Shichao and Luo, Fangzhou and Jin, Li Hua}, doi = {10.1016/j.dci.2017.11.017}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {83}, unique-id = {27602733}, issn = {0145-305X}, year = {2018}, eissn = {1879-0089}, pages = {60-69} } @article{MTMT:26891561, title = {A Genetic Screen Reveals an Unexpected Role for Yorkie Signaling in JAK/STAT-Dependent Hematopoietic Malignancies in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/26891561}, author = {Anderson, Abigail M and Bailetti, Alessandro A and Rodkin, Elizabeth and De, Atish and Bach, Erika A}, doi = {10.1534/g3.117.044172}, journal-iso = {G3-GENES GENOM GENET}, journal = {G3-GENES GENOMES GENETICS}, volume = {7}, unique-id = {26891561}, issn = {2160-1836}, year = {2017}, eissn = {2160-1836}, pages = {2427-2438} } @article{MTMT:3249751, title = {Hemolectin expression reveals functional heterogeneity in honey bee (Apis mellifera) hemocytes}, url = {https://m2.mtmt.hu/api/publication/3249751}, author = {Gábor, Erika and Cinege, Gyöngyi Ilona and Csordás, Gábor and Török, Tibor and Medzihradszky F., Katalin and Darula, Zsuzsanna and Andó, István and Kurucz, Judit Éva}, doi = {10.1016/j.dci.2017.07.013}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {76}, unique-id = {3249751}, issn = {0145-305X}, year = {2017}, eissn = {1879-0089}, pages = {403-411}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Török, Tibor/0000-0002-2128-1126; Andó, István/0000-0002-4648-9396} } @article{MTMT:26674043, title = {The role of variant histone H2AV in Drosophila melanogaster larval hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/26674043}, author = {Grigorian, M and DeBruhl, H and Lipsick, JS}, doi = {10.1242/dev.142729}, journal-iso = {DEVELOPMENT}, journal = {DEVELOPMENT}, volume = {144}, unique-id = {26674043}, issn = {0950-1991}, year = {2017}, eissn = {1477-9129}, pages = {1441-1449} } @article{MTMT:27049998, title = {Insect Antimicrobial Defences: A Brief History, Recent Findings, Biases, and a Way Forward in Evolutionary Studies}, url = {https://m2.mtmt.hu/api/publication/27049998}, author = {Keehnen, Naomi L P and Rolff, Jens and Theopold, Ulrich and Wheat, Christopher W}, doi = {10.1016/bs.aiip.2017.02.003}, editor = {Ligoxygakis, P}, journal-iso = {ADV INSECT PHYSIOL}, journal = {ADVANCES IN INSECT PHYSIOLOGY}, volume = {52}, unique-id = {27049998}, issn = {0065-2806}, year = {2017}, eissn = {2213-6800}, pages = {1-33} } @inbook{MTMT:27048320, title = {Phagocytosis in Insect Immunity}, url = {https://m2.mtmt.hu/api/publication/27048320}, author = {Nazario-Toole, Ashley E and Wu, Louisa P}, booktitle = {Advances in Insect Physiology}, doi = {10.1016/bs.aiip.2016.12.001}, unique-id = {27048320}, year = {2017}, pages = {35-82} } @article{MTMT:27049472, title = {Tumor-promoting function of apoptotic caspases by an amplification loop involving ROS, macrophages and JNK in Drosophila}, url = {https://m2.mtmt.hu/api/publication/27049472}, author = {Perez, Ernesto and Lindblad, Jillian L and Bergmann, Andreas}, doi = {10.7554/eLife.26747}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {6}, unique-id = {27049472}, issn = {2050-084X}, year = {2017}, eissn = {2050-084X}, orcid-numbers = {Bergmann, Andreas/0000-0002-9134-871X} } @article{MTMT:26698808, title = {A Drosophila model of myeloproliferative neoplasm reveals a feed-forward loop in the JAK pathway mediated by p38 MAPK signalling}, url = {https://m2.mtmt.hu/api/publication/26698808}, author = {Terriente-Felix, Ana and Perez, Lidia and Bray, Sarah J and Nebreda, Angel R and Milan, Marco}, doi = {10.1242/dmm.028118}, journal-iso = {DIS MODEL MECH}, journal = {DISEASE MODELS & MECHANISMS}, volume = {10}, unique-id = {26698808}, issn = {1754-8403}, year = {2017}, eissn = {1754-8411}, pages = {399-407}, orcid-numbers = {Milan, Marco/0000-0002-7111-6444} } @article{MTMT:3096913, title = {Transdifferentiation and Proliferation in Two Distinct Hemocyte Lineages in Drosophila melanogaster Larvae after Wasp Infection.}, url = {https://m2.mtmt.hu/api/publication/3096913}, author = {Anderl, I and Vesala, L and Ihalainen, TO and Vanha-Aho, LM and Andó, István and Ramet, M and Hultmark, D}, doi = {10.1371/journal.ppat.1005746}, journal-iso = {PLOS PATHOG}, journal = {PLOS PATHOGENS}, volume = {12}, unique-id = {3096913}, issn = {1553-7366}, abstract = {Cellular immune responses require the generation and recruitment of diverse blood cell types that recognize and kill pathogens. In Drosophila melanogaster larvae, immune-inducible lamellocytes participate in recognizing and killing parasitoid wasp eggs. However, the sequence of events required for lamellocyte generation remains controversial. To study the cellular immune system, we developed a flow cytometry approach using in vivo reporters for lamellocytes as well as for plasmatocytes, the main hemocyte type in healthy larvae. We found that two different blood cell lineages, the plasmatocyte and lamellocyte lineages, contribute to the generation of lamellocytes in a demand-adapted hematopoietic process. Plasmatocytes transdifferentiate into lamellocyte-like cells in situ directly on the wasp egg. In parallel, a novel population of infection-induced cells, which we named lamelloblasts, appears in the circulation. Lamelloblasts proliferate vigorously and develop into the major class of circulating lamellocytes. Our data indicate that lamellocyte differentiation upon wasp parasitism is a plastic and dynamic process. Flow cytometry with in vivo hemocyte reporters can be used to study this phenomenon in detail.}, year = {2016}, eissn = {1553-7374}, pages = {e1005746}, orcid-numbers = {Andó, István/0000-0002-4648-9396} } @article{MTMT:26377269, title = {Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland of Drosophila}, url = {https://m2.mtmt.hu/api/publication/26377269}, author = {Dey, Nidhi Sharma and Ramesh, Parvathy and Chugh, Mayank and Mandal, Sudip and Mandal, Lolitika}, doi = {10.7554/eLife.18295}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {5}, unique-id = {26377269}, issn = {2050-084X}, year = {2016}, eissn = {2050-084X} } @article{MTMT:25771085, title = {Extracellular Reactive Oxygen Species Drive Apoptosis-Induced Proliferation via Drosophila Macrophages}, url = {https://m2.mtmt.hu/api/publication/25771085}, author = {Fogarty, Caitlin E and Diwanji, Neha and Lindblad, Jillian L and Tare, Meghana and Amcheslavsky, Alla and Makhijani, Kalpana and Brueckner, Katja and Fan, Yun and Bergmann, Andreas}, doi = {10.1016/j.cub.2015.12.064}, journal-iso = {CURR BIOL}, journal = {CURRENT BIOLOGY}, volume = {26}, unique-id = {25771085}, issn = {0960-9822}, year = {2016}, eissn = {1879-0445}, pages = {575-584} } @article{MTMT:26016211, title = {The Friend of GATA Transcriptional Co-Regulator, U-Shaped, Is a Downstream Antagonist of Dorsal-Driven Prohemocyte Differentiation in Drosophila}, url = {https://m2.mtmt.hu/api/publication/26016211}, author = {Gao, Hongjuan and Baldeosingh, Rajkumar and Wu, Xiaorong and Fossett, Nancy}, doi = {10.1371/journal.pone.0155372}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {11}, unique-id = {26016211}, issn = {1932-6203}, year = {2016}, eissn = {1932-6203} } @article{MTMT:26377142, title = {Functional characterisation of phagocytes in the Pacific oyster Crassostrea gigas}, url = {https://m2.mtmt.hu/api/publication/26377142}, author = {Jiang, Shuai and Jia, Zhihao and Zhang, Tao and Wang, Lingling and Qiu, Limei and Sun, Jinsheng and Song, Linsheng}, doi = {10.7717/peerj.2590}, journal-iso = {PEERJ}, journal = {PEERJ}, volume = {4}, unique-id = {26377142}, issn = {2167-8359}, year = {2016}, eissn = {2167-8359} } @article{MTMT:3045263, title = {The raspberry Gene Is Involved in the Regulation of the Cellular Immune Response in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/3045263}, author = {Kari, Beáta and Csordás, Gábor and Honti, Viktor and Cinege, Gyöngyi Ilona and Williams, MJ and Andó, István and Kurucz, Judit Éva}, doi = {10.1371/journal.pone.0150910}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {11}, unique-id = {3045263}, issn = {1932-6203}, abstract = {Drosophila is an extremely useful model organism for understanding how innate immune mechanisms defend against microbes and parasitoids. Large foreign objects trigger a potent cellular immune response in Drosophila larva. In the case of endoparasitoid wasp eggs, this response includes hemocyte proliferation, lamellocyte differentiation and eventual encapsulation of the egg. The encapsulation reaction involves the attachment and spreading of hemocytes around the egg, which requires cytoskeletal rearrangements, changes in adhesion properties and cell shape, as well as melanization of the capsule. Guanine nucleotide metabolism has an essential role in the regulation of pathways necessary for this encapsulation response. Here, we show that the Drosophila inosine 5'-monophosphate dehydrogenase (IMPDH), encoded by raspberry (ras), is centrally important for a proper cellular immune response against eggs from the parasitoid wasp Leptopilina boulardi. Notably, hemocyte attachment to the egg and subsequent melanization of the capsule are deficient in hypomorphic ras mutant larvae, which results in a compromised cellular immune response and increased survival of the parasitoid.}, keywords = {PHAGOCYTOSIS; INHIBITORS; ACTIVATION; SCREEN; RHO; Hematopoiesis; INOSINE MONOPHOSPHATE DEHYDROGENASE; Parasitoids; SMALL GTPASES; LEPTOPILINA-BOULARDI}, year = {2016}, eissn = {1932-6203}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:26203993, title = {Functional integration of the circulatory, immune, and respiratory systems in mosquito larvae: pathogen killing in the hemocyte-rich tracheal tufts}, url = {https://m2.mtmt.hu/api/publication/26203993}, author = {League, Garrett P and Hillyer, Julian F}, doi = {10.1186/s12915-016-0305-y}, journal-iso = {BMC BIOL}, journal = {BMC BIOLOGY}, volume = {14}, unique-id = {26203993}, issn = {1741-7007}, year = {2016}, eissn = {1741-7007} } @article{MTMT:30901168, title = {MiniCORVET is a Vps8-containing early endosomal tether in Drosophila}, url = {https://m2.mtmt.hu/api/publication/30901168}, author = {Lőrincz, Péter and Lakatos, Zsolt and Varga, Ágnes and Maruzs, Tamás and Simon-Vecsei, Zsófia Judit and Darula, Zsuzsanna and Benkő, Péter and Csordás, Gábor and Lippai, Mónika and Andó, István and Hegedűs, Krisztina and Medzihradszky F., Katalin and Takáts, Szabolcs and Juhász, Gábor}, doi = {10.7554/eLife.14226}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {5}, unique-id = {30901168}, issn = {2050-084X}, abstract = {Yeast studies identified two heterohexameric tethering complexes, which consist of 4 shared (Vps11, Vps16, Vps18 and Vps33) and 2 specific subunits: Vps3 and Vps8 (CORVET) versus Vps39 and Vps41 (HOPS). CORVET is an early and HOPS is a late endosomal tether. The function of HOPS is well known in animal cells, while CORVET is poorly characterized. Here we show that Drosophila Vps8 is highly expressed in hemocytes and nephrocytes, and localizes to early endosomes despite the lack of a clear Vps3 homolog. We find that Vps8 forms a complex and acts together with Vps16A, Dor/Vps18 and Car/Vps33A, and loss of any of these proteins leads to fragmentation of endosomes. Surprisingly, Vps11 deletion causes enlargement of endosomes, similar to loss of the HOPS-specific subunits Vps39 and Lt/Nps41. We thus identify a 4 subunit-containing miniCORVET complex as an unconventional early endosomal tether in Drosophila.}, year = {2016}, eissn = {2050-084X}, orcid-numbers = {Lőrincz, Péter/0000-0001-7374-667X; Lakatos, Zsolt/0000-0003-1900-3167; Maruzs, Tamás/0000-0001-8142-3221; Simon-Vecsei, Zsófia Judit/0000-0001-7909-4895; Benkő, Péter/0000-0002-2050-7509; Csordás, Gábor/0000-0001-6871-6839; Lippai, Mónika/0000-0002-7307-4233; Andó, István/0000-0002-4648-9396; Takáts, Szabolcs/0000-0003-2139-7740; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:26674053, title = {Methods to examine the lymph gland and hemocytes in Drosophila larvae}, url = {https://m2.mtmt.hu/api/publication/26674053}, author = {Reimels, TA and Pfleger, CM}, doi = {10.3791/54544}, journal-iso = {JOVE-J VIS EXP}, journal = {JOVE-JOURNAL OF VISUALIZED EXPERIMENTS}, volume = {2016}, unique-id = {26674053}, issn = {1940-087X}, year = {2016}, eissn = {1940-087X} } @article{MTMT:26237558, title = {Genetic Screen in Drosophila Larvae Links ird1 Function to Toll Signaling in the Fat Body and Hemocyte Motility}, url = {https://m2.mtmt.hu/api/publication/26237558}, author = {Schmid, Martin R and Anderl, Ines and Vo, Hoa T M and Valanne, Susanna and Yang, Hairu and Kronhamn, Jesper and Ramet, Mika and Rusten, Tor Erik and Hultmark, Dan}, doi = {10.1371/journal.pone.0159473}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {11}, unique-id = {26237558}, issn = {1932-6203}, year = {2016}, eissn = {1932-6203}, orcid-numbers = {Yang, Hairu/0000-0002-9420-878X} } @mastersthesis{MTMT:26827138, title = {Identification of Novel Stat92E Target Genes in Drosophila Hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/26827138}, author = {Vyas, Aditi}, unique-id = {26827138}, year = {2016} } @article{MTMT:26203591, title = {Overexpression of jumu induces melanotic nodules by activating Toll signaling in Drosophila}, url = {https://m2.mtmt.hu/api/publication/26203591}, author = {Zhang, Gaoqun and Hao, Yangguang and Jin, Li Hua}, doi = {10.1016/j.ibmb.2016.08.002}, journal-iso = {INSECT BIOCHEM MOLEC}, journal = {INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY}, volume = {77}, unique-id = {26203591}, issn = {0965-1748}, year = {2016}, eissn = {1879-0240}, pages = {31-38} } @mastersthesis{MTMT:26827134, title = {Activation of the Cellular Immune Response in Drosophila melanogaster Larvae}, url = {https://m2.mtmt.hu/api/publication/26827134}, author = {Anderl, Ines}, unique-id = {26827134}, year = {2015} } @mastersthesis{MTMT:26827132, title = {Ecology and evolution in a host-parasitoid system: Host search, immune responses and parasitoid virulence}, url = {https://m2.mtmt.hu/api/publication/26827132}, author = {Fors, Lisa}, unique-id = {26827132}, year = {2015} } @article{MTMT:24982068, title = {Active Hematopoietic Hubs in Drosophila Adults Generate Hemocytes and Contribute to Immune Response}, url = {https://m2.mtmt.hu/api/publication/24982068}, author = {Ghosh, S and Singh, A and Mandal, S and Mandal, L}, doi = {10.1016/j.devcel.2015.03.014}, journal-iso = {DEV CELL}, journal = {DEVELOPMENTAL CELL}, volume = {33}, unique-id = {24982068}, issn = {1534-5807}, year = {2015}, eissn = {1878-1551}, pages = {478-488} } @article{MTMT:27117294, title = {Macrophages and cellular immunity in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/27117294}, author = {Gold, KS and Brückner, K}, doi = {10.1016/j.smim.2016.03.010}, journal-iso = {SEMIN IMMUNOL}, journal = {SEMINARS IN IMMUNOLOGY}, volume = {27}, unique-id = {27117294}, issn = {1044-5323}, year = {2015}, eissn = {1096-3618}, pages = {357-368} } @article{MTMT:2993019, title = {Innate immunity}, url = {https://m2.mtmt.hu/api/publication/2993019}, author = {Honti, Viktor and Kurucz, Judit Éva and Cinege, Gyöngyi Ilona and Csordás, Gábor and Andó, István}, journal-iso = {ACTA BIOL SZEGED}, journal = {ACTA BIOLOGICA SZEGEDIENSIS}, volume = {59}, unique-id = {2993019}, issn = {1588-385X}, year = {2015}, eissn = {1588-4082}, pages = {1-15}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:24797542, title = {Drosophila sessile hemocyte clusters are true hematopoietic tissues that regulate larval blood cell differentiation}, url = {https://m2.mtmt.hu/api/publication/24797542}, author = {Leitao, Alexandre B and Sucena, Elio}, doi = {10.7554/eLife.06166}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {4}, unique-id = {24797542}, issn = {2050-084X}, abstract = {Virtually all species of coelomate animals contain blood cells that display a division of labor necessary for homeostasis. This functional partition depends upon the balance between proliferation and differentiation mostly accomplished in the hematopoietic organs. In Drosophila melanogaster, the lymph gland produces plasmatocytes and crystal cells that are not released until pupariation. Yet, throughout larval development, both hemocyte types increase in numbers. Mature plasmatocytes can proliferate but it is not known if crystal cell numbers increase by self-renewal or by de novo differentiation. We show that new crystal cells in third instar larvae originate through a Notch-dependent process of plasmatocyte transdifferentiation. This process occurs in the sessile clusters and is contingent upon the integrity of these structures. The existence of this hematopoietic tissue, relying on structure-dependent signaling events to promote blood homeostasis, creates a new paradigm for addressing outstanding questions in Drosophila hematopoiesis and establishing further parallels with vertebrate systems. © 2015, eLife Sciences Publications Ltd. All rights reserved.}, year = {2015}, eissn = {2050-084X}, pages = {1-38} } @article{MTMT:2853634, title = {Multinucleated Giant Hemocytes Are Effector Cells in Cell-Mediated Immune Responses of Drosophila}, url = {https://m2.mtmt.hu/api/publication/2853634}, author = {Márkus, Róbert and Lerner, Zita and Honti, Viktor and Csordás, Gábor and Zsámboki, János and Cinege, Gyöngyi Ilona and Párducz, Árpád and Lukacsovich, Tamás and Kurucz, Judit Éva and Andó, István}, doi = {10.1159/000369618}, journal-iso = {J INNATE IMMUN}, journal = {JOURNAL OF INNATE IMMUNITY}, volume = {7}, unique-id = {2853634}, issn = {1662-811X}, abstract = {We identified and characterized a so far unrecognized cell type, dubbed the multinucleated giant hemocyte (MGH), in the ananassae subgroup of Drosophilidae. Here, we describe the functional and ultrastructural characteristics of this novel blood cell type as well as its characterization with a set of discriminative immunological markers. MGHs are encapsulating cells that isolate and kill the parasite without melanization. They share some properties with but differ considerably from lamellocytes, the encapsulating cells of Drosophila melanogaster, the broadly used model organism in studies of innate immunity. MGHs are nonproliferative effector cells that are derived from phagocytic cells of the sessile tissue and the circulation, but do not exhibit phagocytic activity. In contrast to lamellocytes, MGHs are gigantic cells with filamentous projections and contain many nuclei, which are the result of the fusion of several cells. Although the structure of lamellocytes and MGHs differ remarkably, their function in the elimination of parasites is similar, which is potentially the result of the convergent evolution of interactions between hosts and parasites in different geographic regions. MGHs are highly motile and share several features with mammalian multinucleated giant cells, a syncytium of macrophages formed during granulomatous inflammation. © 2015 S. Karger AG, Basel}, year = {2015}, eissn = {1662-8128}, pages = {340-353}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:25286198, title = {Protection of Insects against Viral Infection by Apoptosis-Dependent Phagocytosis}, url = {https://m2.mtmt.hu/api/publication/25286198}, author = {Nainu, Firzan and Tanaka, Yumiko and Shiratsuchi, Akiko and Nakanishi, Yoshinobu}, doi = {10.4049/jimmunol.1500613}, journal-iso = {J IMMUNOL}, journal = {JOURNAL OF IMMUNOLOGY}, volume = {195}, unique-id = {25286198}, issn = {0022-1767}, year = {2015}, eissn = {1550-6606}, pages = {5696-5706}, orcid-numbers = {Nakanishi, Yoshinobu/0000-0002-8767-3587} } @article{MTMT:25771415, title = {Drosophila Rabex-5 restricts Notch activity in hematopoietic cells and maintains hematopoietic homeostasis}, url = {https://m2.mtmt.hu/api/publication/25771415}, author = {Reimels, Theresa A and Pfleger, Cathie M}, doi = {10.1242/jcs.174433}, journal-iso = {J CELL SCI}, journal = {JOURNAL OF CELL SCIENCE}, volume = {128}, unique-id = {25771415}, issn = {0021-9533}, year = {2015}, eissn = {1477-9137}, pages = {4512-4525} } @article{MTMT:24797539, title = {Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila}, url = {https://m2.mtmt.hu/api/publication/24797539}, author = {Reitman, Zachary J and Sinenko, Sergey A and Spana, Eric P and Yan, Hai}, doi = {10.1182/blood-2014-05-577940}, journal-iso = {BLOOD}, journal = {BLOOD}, volume = {125}, unique-id = {24797539}, issn = {0006-4971}, year = {2015}, eissn = {1528-0020}, pages = {336-345} } @article{MTMT:24797541, title = {Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation}, url = {https://m2.mtmt.hu/api/publication/24797541}, author = {Yamamoto-Hino, Miki and Muraoka, Masatoshi and Kondo, Shu and Ueda, Ryu and Okano, Hideyuki and Goto, Satoshi}, doi = {10.1073/pnas.1424514112}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {112}, unique-id = {24797541}, issn = {0027-8424}, year = {2015}, eissn = {1091-6490}, pages = {5809-5814} } @article{MTMT:24098832, title = {G alpha 73B is a downstream effector of JAK/STAT signalling and a regulator of Rho1 in Drosophila haematopoiesis}, url = {https://m2.mtmt.hu/api/publication/24098832}, author = {Bausek, N and Zeidler, MP}, doi = {10.1242/jcs.132852}, journal-iso = {J CELL SCI}, journal = {JOURNAL OF CELL SCIENCE}, volume = {127}, unique-id = {24098832}, issn = {0021-9533}, year = {2014}, eissn = {1477-9137}, pages = {101-110} } @article{MTMT:2708773, title = {In Vivo Immunostaining of Hemocyte Compartments in Drosophila for Live Imaging}, url = {https://m2.mtmt.hu/api/publication/2708773}, author = {Csordás, Gábor and Varga, Gergely István and Honti, Viktor and Jankovics, Ferenc and Kurucz, Judit Éva and Andó, István}, doi = {10.1371/journal.pone.0098191}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {9}, unique-id = {2708773}, issn = {1932-6203}, abstract = {In recent years, Drosophila melanogaster has become an attractive model organism in which to study the structure and development of the cellular immune components. The emergence of immunological markers greatly accelerated the identification of the immune cells (hemocytes), while the creation of genetic reporter constructs allowed unique insight into the structural organization of hematopoietic tissues. However, investigation of the hemocyte compartments by the means of immunological markers requires dissection and fixation, which regularly disrupt the delicate structure and hamper the microanatomical characterization. Moreover, the investigation of transgenic reporters alone can be misleading as their expression often differs from the native expression pattern of their respective genes. We describe here a method that combines the reporter constructs and the immunological tools in live imaging, thereby allowing use of the array of available immunological markers while retaining the structural integrity of the hematopoietic compartments. The procedure allows the reversible immobilization of Drosophila larvae for high-resolution confocal imaging and the time-lapse video analysis of in vivo reporters. When combined with our antibody injection-based in situ immunostaining assay, the resulting double labeling of the hemocyte compartments can provide new information on the microanatomy and functional properties of the hematopoietic tissues in an intact state. Although this method was developed to study the immune system of Drosophila melanogaster, we anticipate that such a combination of genetic and immunological markers could become a versatile technique for in vivo studies in other biological systems too.}, year = {2014}, eissn = {1932-6203}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Varga, Gergely István/0000-0001-9073-5788; Andó, István/0000-0002-4648-9396} } @article{MTMT:24399547, title = {Drosophila hematopoiesis: Markers and methods for molecular genetic analysis}, url = {https://m2.mtmt.hu/api/publication/24399547}, author = {Evans, CJ and Liu, T and Banerjee, U}, doi = {10.1016/j.ymeth.2014.02.038}, journal-iso = {METHODS}, journal = {METHODS}, volume = {68}, unique-id = {24399547}, issn = {1046-2023}, year = {2014}, eissn = {1095-9130}, pages = {242-251} } @article{MTMT:25561583, title = {Kicking it up a Notch for the best in show: Scalloped leads Yorkie into the haematopoietic arena}, url = {https://m2.mtmt.hu/api/publication/25561583}, author = {Ferguson, Gabriel B and Martinez-Agosto, Julian A}, doi = {10.1080/19336934.2015.1055427}, journal-iso = {FLY}, journal = {FLY}, volume = {8}, unique-id = {25561583}, issn = {1933-6934}, year = {2014}, eissn = {1933-6942}, pages = {206-217} } @article{MTMT:24356904, title = {Differences in Cellular Immune Competence Explain Parasitoid Resistance for Two Coleopteran Species}, url = {https://m2.mtmt.hu/api/publication/24356904}, author = {Fors, L and Markus, R and Theopold, U and Hamback, PA}, doi = {10.1371/journal.pone.0108795}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {9}, unique-id = {24356904}, issn = {1932-6203}, year = {2014}, eissn = {1932-6203} } @article{MTMT:24356254, title = {Antioxidants Maintain E-Cadherin Levels to Limit Drosophila Prohemocyte Differentiation}, url = {https://m2.mtmt.hu/api/publication/24356254}, author = {Gao, HJ and Wu, XR and Simon, L and Fossett, N}, doi = {10.1371/journal.pone.0107768}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {9}, unique-id = {24356254}, issn = {1932-6203}, year = {2014}, eissn = {1932-6203} } @article{MTMT:24355470, title = {Drosophila as a model for the two myeloid blood cell systems in vertebrates}, url = {https://m2.mtmt.hu/api/publication/24355470}, author = {Gold, KS and Bruckner, K}, doi = {10.1016/j.exphem.2014.06.002}, journal-iso = {EXP HEMATOL}, journal = {EXPERIMENTAL HEMATOLOGY}, volume = {42}, unique-id = {24355470}, issn = {0301-472X}, year = {2014}, eissn = {1873-2399}, pages = {717-727} } @article{MTMT:24797548, title = {A Drosophila immune response against Ras-induced overgrowth}, url = {https://m2.mtmt.hu/api/publication/24797548}, author = {Hauling, Thomas and Krautz, Robert and Markus, Robert and Volkenhoff, Anne and Kucerova, Lucie and Theopold, Ulrich}, doi = {10.1242/bio.20146494}, journal-iso = {BIOL OPEN}, journal = {BIOLOGY OPEN}, volume = {3}, unique-id = {24797548}, issn = {2046-6390}, year = {2014}, eissn = {2046-6390}, pages = {250-260} } @article{MTMT:2372553, title = {The cell-mediated immunity of Drosophila melanogaster: Hemocyte lineages, immune compartments, microanatomy and regulation.}, url = {https://m2.mtmt.hu/api/publication/2372553}, author = {Honti, Viktor and Csordás, Gábor and Kurucz, Judit Éva and Márkus, Róbert and Andó, István}, doi = {10.1016/j.dci.2013.06.005}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {42}, unique-id = {2372553}, issn = {0145-305X}, abstract = {In the animal kingdom, innate immunity is the first line of defense against invading pathogens. The dangers of microbial and parasitic attacks are countered by similar mechanisms, involving the prototypes of the cell-mediated immune responses, the phagocytosis and encapsulation. Work on Drosophila has played an important role in promoting an understanding of the basic mechanisms of phylogenetically conserved modules of innate immunity. The aim of this review is to survey the developments in the identification and functional definition of immune cell types and the immunological compartments of Drosophila melanogaster. We focus on the molecular and developmental aspects of the blood cell types and compartments, as well as the dynamics of blood cell development and the immune response. Further advances in the characterization of the innate immune mechanisms in Drosophila will provide basic clues to the understanding of the importance of the evolutionary conserved mechanisms of innate immune defenses in the animal kingdom.}, year = {2014}, eissn = {1879-0089}, pages = {47-56}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:24098277, title = {A common fungal volatile organic compound induces a nitric oxide mediated inflammatory response in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/24098277}, author = {Inamdar, AA and Bennett, JW}, doi = {10.1038/srep03833}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {4}, unique-id = {24098277}, issn = {2045-2322}, year = {2014}, eissn = {2045-2322} } @article{MTMT:24797975, title = {Basement Membrane and Cell Integrity of Self-Tissues in Maintaining Drosophila Immunological Tolerance}, url = {https://m2.mtmt.hu/api/publication/24797975}, author = {Kim, Moon Jong and Choe, Kwang-Min}, doi = {10.1371/journal.pgen.1004683}, journal-iso = {PLOS GENET}, journal = {PLOS GENETICS}, volume = {10}, unique-id = {24797975}, issn = {1553-7390}, year = {2014}, eissn = {1553-7404} } @article{MTMT:24098276, title = {Evolution of a Cellular Immune Response in Drosophila: A Phenotypic and Genomic Comparative Analysis}, url = {https://m2.mtmt.hu/api/publication/24098276}, author = {Salazar-Jaramillo, L and Paspati, A and van de Zande, L and Vermeulen, CJ and Schwander, T and Wertheim, B}, doi = {10.1093/gbe/evu012}, journal-iso = {GENOME BIOL EVOL}, journal = {GENOME BIOLOGY AND EVOLUTION}, volume = {6}, unique-id = {24098276}, issn = {1759-6653}, year = {2014}, pages = {273-289} } @article{MTMT:32913596, title = {An unexpected link between notch signaling and ROS in restricting the differentiation of hematopoietic progenitors in Drosophila}, url = {https://m2.mtmt.hu/api/publication/32913596}, author = {Small, C. and Ramroop, J. and Otazo, M. and Huang, L.H. and Saleque, S. and Govind, S.}, doi = {10.1534/genetics.113.159210}, journal-iso = {GENETICS}, journal = {GENETICS}, volume = {197}, unique-id = {32913596}, issn = {0016-6731}, abstract = {A fundamental question in hematopoietic development is how multipotent progenitors achieve precise identities, while the progenitors themselves maintain quiescence. In Drosophila melanogaster larvae, multipotent hematopoietic progenitors support the production of three lineages, exhibit quiescence in response to cues from a niche, and from their differentiated progeny. Infection by parasitic wasps alters the course of hematopoiesis. Here we address the role of Notch (N) signaling in lamellocyte differentiation in response to wasp infection. We show that Notch activity is moderately high and ubiquitous in all cells of the lymph gland lobes, with crystal cells exhibiting the highest levels. Wasp infection reduces Notch activity, which results in fewer crystal cells and more lamellocytes. Robust lamellocyte differentiation is induced even in N mutants. Using RNA interference knockdown of N, Serrate, and neuralized (neur), and twin clone analysis of a N null allele, we show that all three genes inhibit lamellocyte differentiation. However, unlike its cell-autonomous function in crystal cell development, Notch's inhibitory influence on lamellocyte differentiation is not cell autonomous. High levels of reactive oxygen species in the lymph gland lobes, but not in the niche, accompany NRNAi-induced lamellocyte differentiation and lobe dispersal. Our results define a novel dual role for Notch signaling in maintaining competence for basal hematopoiesis: while crystal cell development is encouraged, lamellocytic fate remains repressed. Repression of Notch signaling in fly hematopoiesis is important for host defense against natural parasitic wasp infections. These findings can serve as a model to understand how reactive oxygen species and Notch signals are integrated and interpreted in vivo. © 2014 by the Genetics Society of America.}, keywords = {Animals; Female; Female; Male; Male; metabolism; GENETICS; immunohistochemistry; CALCIUM-BINDING PROTEINS; ARTICLE; signal transduction; signal transduction; signal transduction; signal peptide; animal; Cell Differentiation; Cell Differentiation; Membrane Proteins; membrane protein; priority journal; controlled study; Cytology; nonhuman; animal tissue; animal experiment; parasitology; RNA Interference; RNA Interference; Drosophila melanogaster; Drosophila melanogaster; protein expression; Reactive oxygen species; reactive oxygen metabolite; reactive oxygen metabolite; cell maturation; hematopoietic stem cell; Receptors, Notch; Intercellular Signaling Peptides and Proteins; lymph node; Hematopoiesis; Hematopoiesis; Hematopoiesis; calcium binding protein; Hematopoietic Stem Cells; hypoxia inducible factor 1alpha; Ubiquitin-Protein Ligases; gene activity; ubiquitin protein ligase; Notch receptor; Notch receptor; Drosophila Proteins; Wasps; Drosophila protein; WASP; null allele; Serrate proteins; neur protein, Drosophila; notch protein, Drosophila}, year = {2014}, eissn = {1943-2631}, pages = {471-483} } @article{MTMT:25022905, title = {Drosophila E-Cadherin Functions in Hematopoietic Progenitors to Maintain Multipotency and Block Differentiation}, url = {https://m2.mtmt.hu/api/publication/25022905}, author = {Gao, Hongjuan and Wu, Xiaorong and Fossett, Nancy}, doi = {10.1371/journal.pone.0074684}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {8}, unique-id = {25022905}, issn = {1932-6203}, year = {2013}, eissn = {1932-6203} } @article{MTMT:23466778, title = {Polydnaviral Ankyrin Proteins Aid Parasitic Wasp Survival by Coordinate and Selective Inhibition of Hematopoietic and Immune NF-kappa B Signaling in Insect Hosts}, url = {https://m2.mtmt.hu/api/publication/23466778}, author = {Gueguen, G and Kalamarz, ME and Ramroop, J and Uribe, J and Govind, S}, doi = {10.1371/journal.ppat.1003580}, journal-iso = {PLOS PATHOG}, journal = {PLOS PATHOGENS}, volume = {9}, unique-id = {23466778}, issn = {1553-7366}, year = {2013}, eissn = {1553-7374} } @article{MTMT:2326115, title = {Drosophila Nimrod proteins bind bacteria}, url = {https://m2.mtmt.hu/api/publication/2326115}, author = {Zsámboki, János and Csordás, Gábor and Honti, Viktor and Pintér, Lajos and Bajusz, Izabella and Galgóczi, László Norbert and Andó, István and Kurucz, Judit Éva}, doi = {10.2478/s11535-013-0183-4}, journal-iso = {CENT EUR J BIOL}, journal = {CENTRAL EUROPEAN JOURNAL OF BIOLOGY}, volume = {8}, unique-id = {2326115}, issn = {1895-104X}, abstract = {Engulfment of foreign particles by phagocytes is initiated by the engagement of phagocytic receptors. We have previously reported that NimC1 is involved in the phagocytosis of bacteria in Drosophila melanogaster. We have identified a family of genes, the Nimrod gene superfamily, encoding characteristic NIM domain containing structural homologues of NimC1. In this work we studied the bacterium-binding properties of the Nimrod proteins by using a novel immunofluorescencebased flow cytometric assay. This method proved to be highly reproducible and suitable for investigations of the bacteriumbinding capacities of putative phagocytosis receptors. We found that NimC1, NimA, NimB1 and NimB2 bind bacteria significantly but differently. In this respect they are similar to other NIM domain containing receptors Eater and Draper.}, year = {2013}, eissn = {1644-3632}, pages = {633-645}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Galgóczi, László Norbert/0000-0002-6976-8910; Andó, István/0000-0002-4648-9396} }