TY - JOUR AU - Prasasya, R.D. AU - Caldwell, B.A. AU - Liu, Z. AU - Wu, S. AU - Leu, N.A. AU - Fowler, J.M. AU - Cincotta, S.A. AU - Laird, D.J. AU - Kohli, R.M. AU - Bartolomei, M.S. TI - Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions JF - DEVELOPMENTAL CELL J2 - DEV CELL PY - 2024 SN - 1534-5807 DO - 10.1016/j.devcel.2024.02.012 UR - https://m2.mtmt.hu/api/publication/34779700 ID - 34779700 N1 - Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States Department of Biomedical Sciences, Center for Animal Transgenesis and Germ Cell Research, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, United States Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States Department of Obstetrics, Gynecology and Reproductive Science, Center for Reproductive Sciences, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 84143, United States Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, United States Export Date: 9 April 2024 CODEN: DCEEB Correspondence Address: Kohli, R.M.; Department of Medicine, United States; email: rkohli@pennmedicine.upenn.edu Correspondence Address: Bartolomei, M.S.; Department of Cell and Developmental Biology, United States; email: bartolom@pennmedicine.upenn.edu AB - Ten-eleven translocation (TET) enzymes iteratively oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during mammalian germline reprogramming remains unresolved due to the inability to decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V). Tet1 knockout and catalytic mutant primordial germ cells (PGCs) fail to erase methylation at select imprinting control regions and promoters of meiosis-associated genes, validating the requirement for the iterative oxidation of 5mC for complete germline reprogramming. TET1V and TET1HxD rescue most hypermethylation of Tet1−/− sperm, suggesting the role of TET1 beyond its oxidative capability. We additionally identify a broader class of hypermethylated regions in Tet1 mutant mouse sperm that depend on TET oxidation for reprogramming. Our study demonstrates the link between TET1-mediated germline reprogramming and sperm methylome patterning. © 2024 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Shatz, O. AU - Fraiberg, M. AU - Isola, D. AU - Das, S. AU - Gogoi, O. AU - Polyansky, A. AU - Shimoni, E. AU - Dadosh, T. AU - Dezorella, N. AU - Wolf, S.G. AU - Elazar, Z. TI - Rim aperture of yeast autophagic membranes balances cargo inclusion with vesicle maturation JF - DEVELOPMENTAL CELL J2 - DEV CELL PY - 2024 SN - 1534-5807 DO - 10.1016/j.devcel.2024.02.002 UR - https://m2.mtmt.hu/api/publication/34773990 ID - 34773990 N1 - Departments of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, 76100, Israel Chemical Research Support, The Weizmann Institute of Science, Rehovot, 76100, Israel Export Date: 6 April 2024 CODEN: DCEEB Correspondence Address: Elazar, Z.; Departments of Biomolecular Sciences, Israel; email: zvulun.elazar@weizmann.ac.il LA - English DB - MTMT ER - TY - JOUR AU - Wang, J. AU - Li, D.-L. AU - Zheng, L.-F. AU - Ren, S. AU - Huang, Z.-Q. AU - Tao, Y. AU - Liu, Z. AU - Shang, Y. AU - Pang, D. AU - Guo, H. AU - Zeng, T. AU - Wang, H.-R. AU - Huang, H. AU - Du, X. AU - Ye, H. AU - Zhou, H.-M. AU - Li, P. AU - Zhao, T.-J. TI - Dynamic palmitoylation of STX11 controls injury-induced fatty acid uptake to promote muscle regeneration JF - DEVELOPMENTAL CELL J2 - DEV CELL VL - 59 PY - 2024 IS - 3 SP - 384 EP - 399.e5 SN - 1534-5807 DO - 10.1016/j.devcel.2023.12.005 UR - https://m2.mtmt.hu/api/publication/34787241 ID - 34787241 N1 - State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Zhongshan Hospital, Fudan University, Shanghai Qi Zhi Institute, Shanghai, 200438, China Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Henan, Zhengzhou, 450001, China State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian, Xiamen, 361102, China Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an Second People's Hospital, Jiangsu, Xuzhou, 220005, China School of Athletic Performance, Shanghai University of Sport, Shanghai, 200438, China Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing, 314006, China Cited By :1 Export Date: 12 April 2024 CODEN: DCEEB Correspondence Address: Zhao, T.-J.; State Key Laboratory of Genetic Engineering, China; email: zhaotj@fudan.edu.cn Chemicals/CAS: 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene, 109511-58-2; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; octanoic acid, 124-07-2, 1984-06-1, 74-81-7; CD36 Antigens; Fatty Acids; Qa-SNARE Proteins; STX11 protein, human Funding details: 21JC1400400 Funding details: National Natural Science Foundation of China, NSFC, 32071150, 32100539, 32125022, 32230053, 92157301 Funding details: National Key Research and Development Program of China, NKRDPC, 2020YFA0803601 Funding text 1: This work was supported by the National Natural Science Foundation of China ( 32230053 , 32125022 , 92157301 , 32100539 , and 32071150 ), the National Key R&D Program of China ( 2020YFA0803601 ), and the Shanghai Basic Research Field Project “Science and Technology Innovation Action Plan” ( 21JC1400400 ). AB - Different types of cells uptake fatty acids in response to different stimuli or physiological conditions; however, little is known about context-specific regulation of fatty acid uptake. Here, we show that muscle injury induces fatty acid uptake in muscle stem cells (MuSCs) to promote their proliferation and muscle regeneration. In humans and mice, fatty acids are mobilized after muscle injury. Through CD36, fatty acids function as both fuels and growth signals to promote MuSC proliferation. Mechanistically, injury triggers the translocation of CD36 in MuSCs, which relies on dynamic palmitoylation of STX11. Palmitoylation facilitates the formation of STX11/SNAP23/VAMP4 SANRE complex, which stimulates the fusion of CD36- and STX11-containing vesicles. Restricting fatty acid supply, blocking fatty acid uptake, or inhibiting STX11 palmitoylation attenuates muscle regeneration in mice. Our studies have identified a critical role of fatty acids in muscle regeneration and shed light on context-specific regulation of fatty acid sensing and uptake. © 2023 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Coppiello, Giulia AU - Barlabe, Paula AU - Moya-Jodar, Marta AU - Abizanda, Gloria AU - Pogontke, Cristina AU - Barreda, Carolina AU - Iglesias, Elena AU - Linares, Javier AU - Arellano-Viera, Estibaliz AU - Larequi, Eduardo AU - Martin-Uriz, Patxi San AU - Carvajal-Vergara, Xonia AU - Pelacho, Beatriz AU - Mazo, Manuel Maria AU - Perez-Pomares, Jose Maria AU - Ruiz-Villalba, Adrian AU - Ullate-Agote, Asier AU - Prosper, Felipe AU - Aranguren, Xabier L. TI - Generation of heart and vascular system in rodents by blastocyst complementation JF - DEVELOPMENTAL CELL J2 - DEV CELL VL - 58 PY - 2024 IS - 24 PG - 23 SN - 1534-5807 DO - 10.1016/j.devcel.2023.10.008 UR - https://m2.mtmt.hu/api/publication/34614992 ID - 34614992 AB - Generating organs from stem cells through blastocyst complementation is a promising approach to meet the clinical need for transplants. In order to generate rejection-free organs, complementation of both parenchymal and vascular cells must be achieved, as endothelial cells play a key role in graft rejection. Here, we used a lineage-specific cell ablation system to produce mouse embryos unable to form both the cardiac and vascular systems. By mouse intraspecies blastocyst complementation, we rescued heart and vascular system development separately and in combination, obtaining complemented hearts with cardiomyocytes and endothelial cells of exogenous origin. Complemented chimeras were viable and reached adult stage, showing normal cardiac function and no signs of histopathological defects in the heart. Furthermore, we implemented the cell ablation system for rat-to-mouse blastocyst complementation, obtaining xenogeneic hearts whose cardiomyocytes were completely of rat origin. These results represent an advance in the experimentation towards the in vivo generation of transplantable organs. LA - English DB - MTMT ER - TY - JOUR AU - Sahu, S. AU - Sahoo, S. AU - Sullivan, T. AU - O'Sullivan, T.N. AU - Turan, S. AU - Albaugh, M.E. AU - Burkett, S. AU - Tran, B. AU - Salomon, D.S. AU - Kozlov, S.V. AU - Koehler, K.R. AU - Jolly, M.K. AU - Sharan, S.K. TI - Spatiotemporal modulation of growth factors directs the generation of multilineage mouse embryonic stem cell-derived mammary organoids JF - DEVELOPMENTAL CELL J2 - DEV CELL VL - 59 PY - 2024 IS - 2 SP - 175 EP - 186.e8 SN - 1534-5807 DO - 10.1016/j.devcel.2023.12.003 UR - https://m2.mtmt.hu/api/publication/34632223 ID - 34632223 N1 - Mouse Cancer Genetics Program (MCGP), Centre for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States Department of Bioengineering, Indian Institute of Science, Bengaluru, 560012, India Centre for Advanced Preclinical Research (CAPR), National Cancer Institute, Frederick, MD 21702, United States Leidos Biomedical Sciences, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA 02115, United States Department of Otolaryngology, Department of Plastic & Oral Surgery, and the F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, United States Export Date: 19 February 2024 CODEN: DCEEB Correspondence Address: Sharan, S.K.; Mouse Cancer Genetics Program (MCGP), United States; email: sharans@mail.nih.gov Chemicals/CAS: Hedgehog Proteins Funding details: National Institutes of Health, NIH Funding details: National Cancer Institute, NCI Funding details: National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIAMS, R01AR075018 Funding details: European Society of Cardiology, ESC Funding details: Department of Science and Technology, Ministry of Science and Technology, India, DST Funding details: Science and Engineering Research Board, SERB Funding details: Infosys Foundation, SB/S2/RJN-049/2018 Funding text 1: We thank Drs. J. Acharya, I. Daar, J. Keller, A. Mishra, E. Sterneck, and L. Tessarollo for their critical comments on the manuscript. We thank all the members of the Sharan lab, J. Lee and A.P. Le from the Koehler lab, and Drs. Senthil Muthuswamy (NCI) and Geoffrey Wahl (Salk Institute) for suggestions on this project. We acknowledge support from Jyoti Shetty from CCR Single-cell sequencing core facility, Dr. S. Lockett from Optical Microscopy and Analysis Lab, Y. Zhao from CCR Bioinformatics core, Dr. E. Conner from CCR Sequencing core, and J. Carrell and M. Karwan from CCR Flow cytometry core. All figures in this manuscript were prepared using Adobe Illustrator v6, and the illustrations were made using a paid subscription to Biorender.com . Funding text 2: We thank Drs. J. Acharya, I. Daar, J. Keller, A. Mishra, E. Sterneck, and L. Tessarollo for their critical comments on the manuscript. We thank all the members of the Sharan lab, J. Lee and A.P. Le from the Koehler lab, and Drs. Senthil Muthuswamy (NCI) and Geoffrey Wahl (Salk Institute) for suggestions on this project. We acknowledge support from Jyoti Shetty from CCR Single-cell sequencing core facility, Dr. S. Lockett from Optical Microscopy and Analysis Lab, Y. Zhao from CCR Bioinformatics core, Dr. E. Conner from CCR Sequencing core, and J. Carrell and M. Karwan from CCR Flow cytometry core. All figures in this manuscript were prepared using Adobe Illustrator v6, and the illustrations were made using a paid subscription to Biorender.com. The Sharan laboratory is funded by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health. M.K.J. is supported by Infosys Foundation, Bangalore, India, and by the Ramanujan Fellowship (SB/S2/RJN-049/2018) supported by Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India. K.R.K. is supported by the National Institute of Arthritis, Musculoskeletal, and Skin Disease (NIAMS), US National Institutes of Health (R01AR075018). S. Sahu and S.K.S. conceived the study; S. Sahu performed all experiments and designed the induction strategy, preliminary bioinformatics analysis, and mouse surgery; S. Sahoo performed the scRNA-seq analysis under the supervision of M.K.J.; T.S. helped with ESC and organoid maintenance, reproducibility, characterization of CRISPR-generated clones, and western blot; T.N.O'S. helped with optimization of single-cell suspension for RNA-seq; S.T. and B.T. performed the single-cell library preparation and sequencing; M.E.A. maintained the mouse colony and assisted S. Sahu with mouse surgery and monitoring of animal health post-surgery; S.B. performed the karyotype analysis; S.V.K. provided Bruce-4 mESC line and generated the Chris-11 mESCs; D.S.S. provided guidance and suggestions on MG differentiation strategies; K.R.K. provided R1 and ATOH1/nGFP ES cell lines, guidance, and suggestions on organoid generation; and S.K.S. supervised the study. S. Sahu and S.K.S. wrote the manuscript, and all authors were involved in the editing. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. AB - Ectodermal appendages, such as the mammary gland (MG), are thought to have evolved from hair-associated apocrine glands to serve the function of milk secretion. Through the directed differentiation of mouse embryonic stem cells (mESCs), here, we report the generation of multilineage ESC-derived mammary organoids (MEMOs). We adapted the skin organoid model, inducing the dermal mesenchyme to transform into mammary-specific mesenchyme via the sequential activation of Bone Morphogenetic Protein 4 (BMP4) and Parathyroid Hormone-related Protein (PTHrP) and inhibition of hedgehog (HH) signaling. Using single-cell RNA sequencing, we identified gene expression profiles that demonstrate the presence of mammary-specific epithelial cells, fibroblasts, and adipocytes. MEMOs undergo ductal morphogenesis in Matrigel and can reconstitute the MG in vivo. Further, we demonstrate that the loss of function in placode regulators LEF1 and TBX3 in mESCs results in impaired skin and MEMO generation. In summary, our MEMO model is a robust tool for studying the development of ectodermal appendages, and it provides a foundation for regenerative medicine and disease modeling. © 2023 LA - English DB - MTMT ER - TY - JOUR AU - Dingwall, Heather L. AU - Tomizawa, Reiko R. AU - Aharoni, Adam AU - Hu, Peng AU - Qiu, Qi AU - Kokalari, Blerina AU - Martinez, Serenity M. AU - Donahue, Joan C. AU - Aldea, Daniel AU - Mendoza, Meryl AU - Glass, Ian A. AU - Wu, Hao AU - Kamberov, Yana G. TI - Sweat gland development requires an eccrine dermal niche and couples two epidermal programs JF - DEVELOPMENTAL CELL J2 - DEV CELL VL - 59 PY - 2024 IS - 1 PG - 20 SN - 1534-5807 DO - 10.1016/j.devcel.2023.11.015 UR - https://m2.mtmt.hu/api/publication/34614804 ID - 34614804 AB - Eccrine sweat glands are indispensable for human thermoregulation and, similar to other mammalian skin appendages, form from multipotent epidermal progenitors. Limited understanding of how epidermal progenitors specialize to form these vital organs has precluded therapeutic efforts toward their regeneration. Herein, we applied single -nucleus transcriptomics to compare the expression content of wild -type, eccrine-forming mouse skin to that of mice harboring a skin -specific disruption of Engrailed 1 (En1), a transcription factor that promotes eccrine gland formation in humans and mice. We identify two concurrent but disproportionate epidermal transcriptomes in the early eccrine anlagen: one that is shared with hair follicles and one that is En1 dependent and eccrine specific. We demonstrate that eccrine development requires the induction of a dermal niche proximal to each developing gland in humans and mice. Our study defines the signatures of eccrine identity and uncovers the eccrine dermal niche, setting the stage for targeted regeneration and comprehensive skin repair. LA - English DB - MTMT ER - TY - JOUR AU - Collinet, Claudio AU - Bailles, Anais AU - Dehapiot, Benoi AU - Lecuit, Thomas TI - Article Mechanical regulation of substrate adhesion and de-adhesion drives a cell-contractile wave during Drosophila tissue morphogenesis JF - DEVELOPMENTAL CELL J2 - DEV CELL VL - 59 PY - 2024 IS - 1 PG - 25 SN - 1534-5807 DO - 10.1016/j.devcel.2023.11.022 UR - https://m2.mtmt.hu/api/publication/34588944 ID - 34588944 N1 - Aix Marseille Université & CNRS, IBDM - UMR7288 & Turing Centre for Living Systems, Campus de Luminy Case 907, Marseille, 13288, France Collège de France, 11 Place Marcelin Berthelot, Paris, France Export Date: 27 March 2024 CODEN: DCEEB Correspondence Address: Collinet, C.; Aix Marseille Université & CNRS, France; email: claudio.collinet@univ-amu.fr Correspondence Address: Lecuit, T.; Aix Marseille Université & CNRS, France; email: thomas.lecuit@univ-amu.fr AB - During morphogenesis, mechanical forces induce large-scale deformations; yet, how forces emerge from cellular contractility and adhesion is unclear. In Drosophila embryos, a tissue-scale wave of actomyosin contractility coupled with adhesion to the surrounding vitelline membrane drives polarized tissue invagina-tion. We show that this process emerges subcellularly from the mechanical coupling between myosin II acti-vation and sequential adhesion/de-adhesion to the vitelline membrane. At the wavefront, integrin clusters an-chor the actin cortex to the vitelline membrane and promote activation of myosin II, which in turn enhances adhesion in a positive feedback. Following cell detachment, cortex contraction and advective flow amplify myosin II. Prolonged contact with the vitelline membrane prolongs the integrin-myosin II feedback, increases integrin adhesion, and thus slows down cell detachment and wave propagation. The angle of cell detachment depends on adhesion strength and sets the tensile forces required for detachment. Thus, we document how the interplay between subcellular mechanochemical feedback and geometry drives tissue morphogenesis. LA - English DB - MTMT ER - TY - JOUR AU - Sun, Jiaqi AU - Shao, Yang AU - Wang, Songyang AU - Li, Xunzheng AU - Feng, Shuqing AU - Wang, Weina AU - Leroy, Pierre AU - Li, Chengyang AU - Zheng, Huanquan TI - An Arabidopsis Rab18 GTPase promotes autophagy by tethering ATG18a to the ER in response to nutrient starvation JF - DEVELOPMENTAL CELL J2 - DEV CELL PY - 2023 SN - 1534-5807 DO - 10.1016/j.devcel.2023.11.006 UR - https://m2.mtmt.hu/api/publication/34430834 ID - 34430834 N1 - Key Laboratory of Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Shandong, Qingdao, 266237, China Department of Biology, McGill University, Montreal, QC H3B 1A1, Canada Key Laboratory of Horticultural Plant Biology, Ministry of Education, Huazhong Agricultural University, Hubei, Wuhan, 430070, China Cited By :1 Export Date: 21 February 2024 CODEN: DCEEB Correspondence Address: Sun, J.; Key Laboratory of Plant Development and Environmental Adaptation Biology, Shandong, China; email: jiaqi.sun@sdu.edu.cn Correspondence Address: Zheng, H.; Department of Biology, Canada; email: hugo.zheng@mcgill.ca LA - English DB - MTMT ER - TY - JOUR AU - Chen, Qiyu AU - Leshkowitz, Dena AU - Li, Hanjie AU - van Impel, Andreas AU - Schulte-Merker, Stefan AU - Amit, Ido AU - Rizzoti, Karine AU - Levkowitz, Gil TI - Neural plate progenitors give rise to both anterior and posterior pituitary cells JF - DEVELOPMENTAL CELL J2 - DEV CELL PY - 2023 SN - 1534-5807 DO - 10.1016/j.devcel.2023.08.018 UR - https://m2.mtmt.hu/api/publication/34133813 ID - 34133813 LA - English DB - MTMT ER - TY - JOUR AU - Zhu, H. AU - Wang, G. AU - Nguyen-Ngoc, K.-V. AU - Kim, D. AU - Miller, M. AU - Goss, G. AU - Kovsky, J. AU - Harrington, A.R. AU - Saunders, D.C. AU - Hopkirk, A.L. AU - Melton, R. AU - Powers, A.C. AU - Preissl, S. AU - Spagnoli, F.M. AU - Gaulton, K.J. AU - Sander, M. TI - Understanding cell fate acquisition in stem-cell-derived pancreatic islets using single-cell multiome-inferred regulomes JF - DEVELOPMENTAL CELL J2 - DEV CELL VL - 58 PY - 2023 IS - 9 SP - 727 EP - 743.e11 SN - 1534-5807 DO - 10.1016/j.devcel.2023.03.011 UR - https://m2.mtmt.hu/api/publication/33833902 ID - 33833902 N1 - Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0653, United States Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA, United States Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States Centre for Gene Therapy and Regenerative Medicine, King's College London, London, SE1 9RT, United Kingdom Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-0475, United States Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, United States VA Tennessee Valley Healthcare System, Nashville, TN 37212-2637, United States Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, United States Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States Cited By :1 Export Date: 19 May 2023 CODEN: DCEEB Correspondence Address: Sander, M.; Department of Pediatrics, United States; email: maike.sander@mdc-berlin.de AB - Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem-cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and pancreas from childhood and adult donors for comparison. We delineate major cell types, define their regulomes, and describe spatiotemporal gene regulatory relationships between transcription factors. CDX2 emerged as a regulator of enterochromaffin-like cells, which we show resemble a transient, previously unrecognized, serotonin-producing pre-β cell population in fetal pancreas, arguing against a proposed non-pancreatic origin. Furthermore, we observe insufficient activation of signal-dependent transcriptional programs during in vitro β cell maturation and identify sex hormones as drivers of β cell proliferation in childhood. Altogether, our analysis provides a comprehensive understanding of cell fate acquisition in stem-cell-derived islets and a framework for manipulating cell identities and maturity. © 2023 Elsevier Inc. LA - English DB - MTMT ER -