https://m2.mtmt.hu/ hun 2026-09-22 02:45 JournalArticle 34847005 ADMIN_APPROVED true 0 false 2026-07-14T09:54:55.349+0000 2024-12-09T08:59:41.313+0000 2024-05-10T08:12:04.346+0000 true 10080205 Szalóky-Siki Ágnes /api/admin/10080205 Admin true 2024-12-09T08:59:24.250+0000 2024-12-09T08:59:24.250+0000 2024-12-09T08:59:41.319+0000 true 10014568 Vándor Andrea /api/admin/10014568 Admin true 10014568 Admin 10014568 /api/admin/10014568 Vándor Andrea true 10014568 true 2025-05-07T09:27:06.709+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Spathopoulou, Angeliki Integrative metabolomics-genomics analysis identifies key networks in a stem cell-based model of schizophrenia true true /api/journal/14166 REVIEWED true false 14166 false 14166 true 1359-4184 1476-5578 Journal FOREIGN 29 3128 3140 3128 13 2024 Schizophrenia (SCZ) is a neuropsychiatric disorder, caused by a combination of genetic and environmental factors. The etiology behind the disorder remains elusive although it is hypothesized to be associated with the aberrant response to neurotransmitters, such as dopamine and glutamate. Therefore, investigating the link between dysregulated metabolites and distorted neurodevelopment holds promise to offer valuable insights into the underlying mechanism of this complex disorder. In this study, we aimed to explore a presumed correlation between the transcriptome and the metabolome in a SCZ model based on patient-derived induced pluripotent stem cells (iPSCs). For this, iPSCs were differentiated towards cortical neurons and samples were collected longitudinally at various developmental stages, reflecting neuroepithelial-like cells, radial glia, young and mature neurons. The samples were analyzed by both RNA-sequencing and targeted metabolomics and the two modalities were used to construct integrative networks in silico. This multi-omics analysis revealed significant perturbations in the polyamine and gamma-aminobutyric acid (GABA) biosynthetic pathways during rosette maturation in SCZ lines. We particularly observed the downregulation of the glutamate decarboxylase encoding genes GAD1 and GAD2, as well as their protein product GAD65/67 and their biochemical product GABA in SCZ samples. Inhibition of ornithine decarboxylase resulted in further decrease of GABA levels suggesting a compensatory activation of the ornithine/putrescine pathway as an alternative route for GABA production. These findings indicate an imbalance of cortical excitatory/inhibitory dynamics occurring during early neurodevelopmental stages in SCZ. Our study supports the hypothesis of disruption of inhibitory circuits to be causative for SCZ and establishes a novel in silico approach that enables for integrative correlation of metabolic and transcriptomic data of psychiatric disease models. true 2024 true true true false true false NONE 2026-07-14 false 10 0 10 10 0 10 10 9 9 10 10 10 10 10 0 0 10 10 10 10 0 0 0 Folyóiratcikk Journal Article 24 10 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract true true 17 true IDENTICAL 38684795 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=38684795&dopt=Abstract false true Keyword 2068 /api/keyword/2068 true 2068 true Keyword 4679 /api/keyword/4679 true 4679 true Keyword 1084077 /api/keyword/1084077 true 1084077 true Keyword 1305426 /api/keyword/1305426 true 1305426 true Keyword 1493330 /api/keyword/1493330 true true SjrRating 11447135 /api/sjrrating/11447135 4 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr true true ClassificationExternal 2804 /api/classificationexternal/2804 true 2804 true D1 DIRECT true true /api/publication/34847005 <div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <div class="autype autype0"> <span class="author-name" >Spathopoulou Angeliki </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Sauerwein Gabriella A.<sup>*</sup> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Marteau Valentin<sup>*</sup> </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Podlesnic Martina </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Lindlbauer Theresa </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kipura Tobias </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Hotze Madlen </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Gabassi Elisa </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kruszewski Katharina </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Koskuvi Marja </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10021998"><a href="/gui2/?type=authors&mode=browse&sel=10021998" target="_blank">Rethelyi Janos M. (<span class="authorship-author-name">Réthelyi János</span> <span class="authorAux-mtmt"> Pszichiátria- kognítiv idegtudomány</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/Pszichiátriai és Pszichoterápiás Klinika</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10027529"><a href="/gui2/?type=authors&mode=browse&sel=10027529" target="_blank">Apati Agota (<span class="authorship-author-name">Apáti Ágota</span> <span class="authorAux-mtmt"> Őssejt kutatás</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Természettudományi Kutatóközpont">HRN TTK</span>/Molekuláris Élettudományi Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Conti Luciano </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Ku Manching </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Koal Therese </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Mueller Udo </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Talmazan Radu A. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Ojansuu Ilkka </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Vaurio Olli </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Lahteenvuo Markku </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Lehtonen Sarka </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Mertens Jerome </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kwiatkowski Marcel </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Gunther Katharina </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Tiihonen Jari </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Koistinaho Jari </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Trajanoski Zlatko </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Edenhofer Frank ✉ </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;34847005" target="_blank">Integrative metabolomics-genomics analysis identifies key networks in a stem cell-based model of schizophrenia</a></div> <div> <span class="journal-title">MOLECULAR PSYCHIATRY</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1359-4184">1359-4184</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1476-5578">1476-5578</a>)</span>: <span class="journal-volume">29</span> <span class="page"> pp 3128-3140 </span> <span class="year">(2024)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1038/s41380-024-02568-8" target="_blank" href="https://doi.org/10.1038/s41380-024-02568-8"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001209533200002" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001209533200002"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85191800350" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85191800350"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="38684795" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=38684795&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Cellular and Molecular Neuroscience&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Psychiatry and Mental Health&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 10</span> | Független: 10 | Függő: 0 | Nem jelölt: 0 | WoS jelölt: 9 | Scopus jelölt:&nbsp;9 | WoS/Scopus jelölt:&nbsp;10 | DOI jelölt:&nbsp;10 </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 34847005</span> | <span class="status-data status-ADMIN_APPROVED"> Admin láttamozott </span> Forrás | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">WOS TAGGED</span> </div> <div class="lastModified">Utolsó módosítás: 2024.12.09. 09:59 Vándor Andrea (VA, admin) </div> <div class="lockedBy">Központi kezelésű 2025.05.07. 11:27 Vándor Andrea (VA, admin) </div> </div></div>