{"authors":[{"id":"orcid_______::50eeb6c6b3730d42ee961d59a9a9b421","fullName":"Man-Hsin Chang","name":"Man-Hsin","surname":"Chang","rank":1,"pid":{"id":{"scheme":"orcid","value":"0009-0009-4939-2547"},"provenance":null}},{"id":null,"fullName":"Jan Benedikt Waldeck","name":"Jan Benedikt","surname":"Waldeck","rank":2,"pid":{"id":{"scheme":"orcid_pending","value":"0009-0001-5225-9933"},"provenance":null}},{"id":"orcid_______::7ac4111bd1a7871bc88e208e915fec2b","fullName":"Marius Stephan","name":"Marius","surname":"Stephan","rank":3,"pid":{"id":{"scheme":"orcid","value":"0000-0003-1889-3049"},"provenance":null}},{"id":"orcid_______::52a1ed74f4b6e430eb5f9063c2050dad","fullName":"Nirmal Kannaiyan","name":"Nirmal","surname":"Kannaiyan","rank":4,"pid":{"id":{"scheme":"orcid","value":"0000-0002-7408-6842"},"provenance":null}},{"id":null,"fullName":"Valéria de Almeida","name":"Valéria","surname":"de Almeida","rank":5,"pid":null},{"id":"orcid_______::fa36a207fdaf0957fd403de82d767139","fullName":"Emanuel Boudriot","name":"Emanuel","surname":"Boudriot","rank":6,"pid":{"id":{"scheme":"orcid","value":"0000-0001-6083-6318"},"provenance":null}},{"id":null,"fullName":"Temmuz Karali","name":"Temmuz","surname":"Karali","rank":7,"pid":null},{"id":null,"fullName":"Lukas Röll","name":"Lukas","surname":"Röll","rank":8,"pid":{"id":{"scheme":"orcid_pending","value":"0000-0002-0284-2290"},"provenance":null}},{"id":"orcid_______::2b40be9b3bee90d570d975349a36f140","fullName":"Laura Fischer","name":"Laura","surname":"Fischer","rank":9,"pid":{"id":{"scheme":"orcid","value":"0000-0001-8752-5827"},"provenance":null}},{"id":null,"fullName":"Damianos Demetriou","name":"Damianos","surname":"Demetriou","rank":10,"pid":null},{"id":null,"fullName":"Nadia Gabellini","name":"Nadia","surname":"Gabellini","rank":11,"pid":null},{"id":null,"fullName":"Sabrina Galinski","name":"Sabrina","surname":"Galinski","rank":12,"pid":null},{"id":null,"fullName":"Andrea Schmitt","name":"Andrea","surname":"Schmitt","rank":13,"pid":{"id":{"scheme":"orcid_pending","value":"0000-0002-5426-4023"},"provenance":null}},{"id":"orcid_______::ded5ca630c3bec048cfdf3a0dd4d9ba3","fullName":"Sergi Papiol","name":"Sergi","surname":"Papiol","rank":14,"pid":{"id":{"scheme":"orcid","value":"0000-0001-9366-8728"},"provenance":null}},{"id":"orcid_______::8fe3cf1d92efa59ce2c15d6e19b0f4a7","fullName":"Daniel Keeser","name":"Daniel","surname":"Keeser","rank":15,"pid":{"id":{"scheme":"orcid","value":"0000-0002-0244-1024"},"provenance":null}},{"id":null,"fullName":"Peter Falkai","name":"Peter","surname":"Falkai","rank":16,"pid":{"id":{"scheme":"orcid_pending","value":"0000-0003-2873-8667"},"provenance":null}},{"id":null,"fullName":"Moritz J. Rossner","name":"Moritz J.","surname":"Rossner","rank":17,"pid":{"id":{"scheme":"orcid_pending","value":"0000-0002-0667-3420"},"provenance":null}},{"id":"orcid_______::f8a0a6539fa50d54ae9b853faf475d7a","fullName":"Florian J. Raabe","name":"Florian J.","surname":"Raabe","rank":18,"pid":{"id":{"scheme":"orcid","value":"0000-0001-8538-0783"},"provenance":null}}],"openAccessColor":"gold","publiclyFunded":false,"eoscIfGuidelines":null,"type":"publication","language":{"code":"eng","label":"English"},"countries":null,"subjects":[{"subject":{"scheme":"keyword","value":"Male"},"provenance":null},{"subject":{"scheme":"keyword","value":"Adult"},"provenance":null},{"subject":{"scheme":"FOS","value":"0303 health sciences"},"provenance":null},{"subject":{"scheme":"FOS","value":"03 medical and health sciences"},"provenance":null},{"subject":{"scheme":"keyword","value":"Oligodendroglia"},"provenance":null},{"subject":{"scheme":"keyword","value":"Diffusion Tensor Imaging"},"provenance":null},{"subject":{"scheme":"keyword","value":"Induced Pluripotent Stem Cells"},"provenance":null},{"subject":{"scheme":"keyword","value":"Schizophrenia"},"provenance":null},{"subject":{"scheme":"keyword","value":"Humans"},"provenance":null},{"subject":{"scheme":"keyword","value":"Female"},"provenance":null},{"subject":{"scheme":"keyword","value":"Middle Aged"},"provenance":null},{"subject":{"scheme":"keyword","value":"White Matter"},"provenance":null},{"subject":{"scheme":"keyword","value":"Article"},"provenance":null}],"mainTitle":"iPSC-modelling reveals genetic associations and morphological alterations of oligodendrocytes in schizophrenia","subTitle":null,"descriptions":["<jats:title>Abstract</jats:title>           <jats:p>There is strong evidence for a genetically driven neuronal contribution in schizophrenia (SCZ). Although imaging and postmortem studies also provide evidence for white matter alterations with implications of the oligodendroglial lineage in SCZ, it is unclear whether these disturbances are a secondary consequence of neuronal deficits or also, at least in parts, genetically driven and cell-autonomous. Using human induced pluripotent stem cells (hiPSCs) in combination with gene set enrichment analysis, we investigated the cellular impact of SCZ genetics on the oligodendroglial lineage. We performed unsupervised clustering analysis of hiPSC-differentiated neural cells including oligodendrocytes (iOLs) and their precursor cells (iOPCs) with corresponding human postmortem cell types from single-cell RNA sequencing (scRNAseq) data and conducted a comparative gene set enrichment analysis. Subsequently, we stratified individuals based on white matter alteration using diffusion tensor imaging (DTI) within a translational cohort (N = 112) and then explored the cellular effects of SCZ risk with hiPSC modelling in a subset of SCZ patients (N = 8) with disturbed white matter integrity and unaffected healthy controls (N = 7). hiPSC-iOPCs/iOLs expression profiles strongly correlated with human postmortem OPCs/OLs based on scRNAseq, and their transcriptional signatures were highly enriched in the genetic associations of SCZ. The cellular assessment of patient-derived iOPCs/iOLs revealed morphological alterations, including significantly increased branch length and elevated junction number in mature iOLs from SCZ. Moreover, transcriptomic profiling revealed a dysregulation in oligodendroglial cell signaling and proliferation. In sum, hiPSC-modelling shows an impact of SCZ genetics on dedicated features of the oligodendroglial lineage.</jats:p>"],"publicationDate":"2025-08-16","publisher":"Springer Science and Business Media LLC","embargoEndDate":null,"sources":["Crossref","Transl Psychiatry","Translational Psychiatry"],"formats":["application/pdf"],"contributors":null,"coverages":null,"bestAccessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/"},"container":{"name":"Translational Psychiatry","issnPrinted":null,"issnOnline":"2158-3188","issnLinking":null,"ep":null,"iss":null,"sp":null,"vol":"15","edition":null,"conferencePlace":null,"conferenceDate":null},"documentationUrls":null,"codeRepositoryUrl":null,"programmingLanguage":null,"contactPeople":null,"contactGroups":null,"tools":null,"size":null,"version":null,"geoLocations":null,"id":"doi_dedup___::9e8b4fb5bf85521d3fb88823311d686d","originalIds":["3509","10.1038/s41398-025-03509-x","50|doiboost____|9e8b4fb5bf85521d3fb88823311d686d","od_______267::ef9add0fbe3696efce860dfeabafc257","40819083","PMC12357907","50|od_______267::ef9add0fbe3696efce860dfeabafc257","oai:pubmedcentral.nih.gov:12357907","50|od______1874::a768320dc89cf7e721b15c9df113d4d8","oai:pure.mpg.de:item_3667331","50|sygma_______::9e8b4fb5bf85521d3fb88823311d686d"],"pids":[{"scheme":"doi","value":"10.1038/s41398-025-03509-x"},{"scheme":"pmid","value":"40819083"},{"scheme":"pmc","value":"PMC12357907"},{"scheme":"handle","value":"21.11116/0000-0011-B13C-2"},{"scheme":"handle","value":"21.11116/0000-0012-82A3-0"}],"dateOfCollection":null,"lastUpdateTimeStamp":null,"indicators":{"citationImpact":{"citationCount":3.0,"influence":2.2473554E-9,"popularity":4.2426747E-9,"impulse":3.0,"citationClass":"C5","influenceClass":"C5","impulseClass":"C5","popularityClass":"C4"}},"projects":[{"id":"corda_____he::b08a003ad24942a4266996265199b7ae","code":"101057454","acronym":"Psych-STRATA","title":"Psych-STRATA - A Stratified Treatment Algorithm in Psychiatry: A program on stratified pharmacogenomics in severe mental illness","funder":"European Commission","pids":[{"scheme":"doi","value":"10.3030/101057454"}]},{"id":"corda_____he::6c34a6f838e437b7092850942dfb9e07","code":"101188432","acronym":"DTRIP4H","title":"Enabling Decentralised Digital Twin Era in existing Research Infrastructures for Predictive, Preventive, Personalised, and Participatory Health","funder":"European Commission","pids":[{"scheme":"doi","value":"10.3030/101188432"}]}],"organizations":[{"legalName":"University of Münster","acronym":"WWU","id":"openorgs____::91ad861541a12e9823ad21841d47879d","pids":[{"scheme":"RRID","value":"RRID:SCR_011687"},{"scheme":"fundref","value":"501100004869"},{"scheme":"Wikidata","value":"Q168426"},{"scheme":"wikidata","value":"Q168426"},{"scheme":"OrgRef","value":"172246"},{"scheme":"PIC","value":"999853691"},{"scheme":"ISNI","value":"0000000121729288"},{"scheme":"fundref","value":"501100004870"},{"scheme":"ROR","value":"https://ror.org/00pd74e08"},{"scheme":"mag_id","value":"22465464"},{"scheme":"FundRef","value":"501100004870"},{"scheme":"FundRef","value":"501100004869"},{"scheme":"GRID","value":"grid.5949.1"}]},{"legalName":"Ludwig-Maximilians-Universität München","acronym":"LMU","id":"openorgs____::a3caad3e06b6235bdbfe47b3d0568909","pids":[{"scheme":"PIC","value":"999978433"},{"scheme":"RRID","value":"RRID:SCR_011358"},{"scheme":"FundRef","value":"501100014999"},{"scheme":"OrgReg","value":"DE0021"},{"scheme":"ISNI","value":"000000041936973X"},{"scheme":"FundRef","value":"501100005722"},{"scheme":"mag_id","value":"8204097"},{"scheme":"Wikidata","value":"Q55044"},{"scheme":"OrgRef","value":"252750"},{"scheme":"RRID","value":"RRID:nlx_28705"},{"scheme":"fundref","value":"501100014999"},{"scheme":"fundref","value":"501100006192"},{"scheme":"FundRef","value":"501100009401"},{"scheme":"wikidata","value":"Q55044"},{"scheme":"GRID","value":"grid.5252.0"},{"scheme":"fundref","value":"501100005722"},{"scheme":"fundref","value":"501100009401"},{"scheme":"ROR","value":"https://ror.org/05591te55"},{"scheme":"FundRef","value":"501100006192"}]},{"legalName":"Deutsches Zentrum für Psychische Gesundheit","acronym":"DZPG","id":"pending_org_::d488828f9c5291ebbfc810f05c90d06c","pids":[{"scheme":"ROR","value":"https://ror.org/00tkfw097"},{"scheme":"ISNI","value":"0000000514299549"}]},{"legalName":"Universidade de São Paulo","acronym":"USP","id":"openorgs____::0e7255aa01f2c42b8175b81d5d084894","pids":[{"scheme":"ROR","value":"https://ror.org/03vrj4p82"},{"scheme":"ROR","value":"https://ror.org/00ttbwp87"},{"scheme":"FundRef","value":"501100005640"},{"scheme":"fundref","value":"501100007386"},{"scheme":"Wikidata","value":"Q835960"},{"scheme":"wikidata","value":"Q7894387"},{"scheme":"ISNI","value":"0000000105795912"},{"scheme":"fundref","value":"501100005639"},{"scheme":"GRID","value":"grid.428481.3"},{"scheme":"wikidata","value":"Q4384447"},{"scheme":"ISNI","value":"000000012112182X"},{"scheme":"Wikidata","value":"Q4384447"},{"scheme":"FundRef","value":"501100007387"},{"scheme":"GRID","value":"grid.412268.b"},{"scheme":"wikidata","value":"Q7894396"},{"scheme":"GRID","value":"grid.442227.5"},{"scheme":"GRID","value":"grid.456932.f"},{"scheme":"GRID","value":"grid.442225.7"},{"scheme":"FundRef","value":"501100005639"},{"scheme":"FundRef","value":"100018217"},{"scheme":"fundref","value":"501100007387"},{"scheme":"OrgRef","value":"3909453"},{"scheme":"OrgRef","value":"32718792"},{"scheme":"wikidata","value":"Q48872290"},{"scheme":"OrgRef","value":"22998677"},{"scheme":"Wikidata","value":"Q7894387"},{"scheme":"wikidata","value":"Q10274618"},{"scheme":"ROR","value":"https://ror.org/02k5swt12"},{"scheme":"ISNI","value":"0000000102984494"},{"scheme":"Wikidata","value":"Q48872290"},{"scheme":"GRID","value":"grid.411249.b"},{"scheme":"FundRef","value":"501100007386"},{"scheme":"ISNI","value":"0000000115163599"},{"scheme":"ROR","value":"https://ror.org/012mm7y56"},{"scheme":"wikidata","value":"Q5428833"},{"scheme":"OrgRef","value":"23565751"},{"scheme":"ISNI","value":"0000000122951681"},{"scheme":"Wikidata","value":"Q10302858"},{"scheme":"Wikidata","value":"Q10274618"},{"scheme":"wikidata","value":"Q10387876"},{"scheme":"ROR","value":"https://ror.org/02sfdnr59"},{"scheme":"ROR","value":"https://ror.org/012gg9483"},{"scheme":"ISNI","value":"0000000419370722"},{"scheme":"Wikidata","value":"Q5428833"},{"scheme":"wikidata","value":"Q593710"},{"scheme":"fundref","value":"501100020987"},{"scheme":"Wikidata","value":"Q48872581"},{"scheme":"wikidata","value":"Q48872581"},{"scheme":"Wikidata","value":"Q10387876"},{"scheme":"wikidata","value":"Q10302858"},{"scheme":"fundref","value":"501100005640"},{"scheme":"FundRef","value":"501100020987"},{"scheme":"OrgRef","value":"561499"},{"scheme":"Wikidata","value":"Q7894396"},{"scheme":"fundref","value":"100018217"},{"scheme":"GRID","value":"grid.11899.38"},{"scheme":"fundref","value":"501100005638"},{"scheme":"ROR","value":"https://ror.org/036rp1748"},{"scheme":"Wikidata","value":"Q593710"},{"scheme":"OrgRef","value":"2336382"},{"scheme":"ISNI","value":"0000000105147202"},{"scheme":"wikidata","value":"Q835960"},{"scheme":"FundRef","value":"501100005638"}]},{"legalName":"Max Planck Society","acronym":"MPG","id":"openorgs____::5a405a89387d1881afa956f475994e10","pids":[{"scheme":"ISNI","value":"0000000121051091"},{"scheme":"ROR","value":"https://ror.org/01hhn8329"},{"scheme":"GRID","value":"grid.4372.2"},{"scheme":"PIC","value":"999990267"},{"scheme":"RRID","value":"RRID:nlx_55250"},{"scheme":"FundRef","value":"501100004189"},{"scheme":"RRID","value":"RRID:SCR_011366"},{"scheme":"Wikidata","value":"Q158085"},{"scheme":"OrgRef","value":"614753"},{"scheme":"mag_id","value":"149899117"},{"scheme":"wikidata","value":"Q158085"},{"scheme":"fundref","value":"501100004189"}]},{"legalName":"Max Planck Institute of Psychiatry","acronym":"Max Planck Institute of Psychiatry","id":"openorgs____::507708e25c210c93371102915d5324b9","pids":[{"scheme":"Wikidata","value":"Q1912091"},{"scheme":"OrgRef","value":"18710375"},{"scheme":"GRID","value":"grid.419548.5"},{"scheme":"ROR","value":"https://ror.org/04dq56617"},{"scheme":"wikidata","value":"Q1912091"},{"scheme":"ISNI","value":"0000000094975095"}]},{"legalName":"Institut für Psychiatrische Phänomik und Genomik","acronym":"IPPG","id":"pending_org_::12dc57370bf3ad95ddd8a5d7bd664827","pids":[{"scheme":"ROR","value":"https://ror.org/0029hqx58"}]}],"communities":[{"code":"neuroscience","label":"Neuroscience","provenance":null}],"collectedFrom":[{"key":"openaire____::a8db6f6b2ce4fe72e8b2314a9a93e7d9","value":"Sygma"},{"key":"opendoar____::958adb57686c2fdec5796398de5f317a","value":"MPG.PuRe"},{"key":"openaire____::081b82f96300b6a6e3d282bad31cb6e2","value":"Crossref"},{"key":"opendoar____::8b6dd7db9af49e67306feb59a8bdc52c","value":"Europe PubMed Central"},{"key":"opendoar____::eda80a3d5b344bc40f3bc04f65b7a357","value":"PubMed Central"}],"instances":[{"pids":[{"scheme":"doi","value":"10.1038/s41398-025-03509-x"}],"license":"CC BY","accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":"gold"},"type":"Article","urls":["https://doi.org/10.1038/s41398-025-03509-x"],"publicationDate":"2025-08-16","refereed":"peerReviewed","hostedBy":{"key":"doajarticles::55c591cd7491eb12cb76474ffa5ee51f","value":"Translational Psychiatry"},"collectedFrom":{"key":"openaire____::081b82f96300b6a6e3d282bad31cb6e2","value":"Crossref"}},{"pids":[{"scheme":"pmid","value":"40819083"},{"scheme":"pmc","value":"PMC12357907"}],"alternateIdentifiers":[{"scheme":"doi","value":"10.1038/s41398-025-03509-x"}],"accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":"gold"},"type":"Article","urls":["https://pubmed.ncbi.nlm.nih.gov/40819083"],"publicationDate":"2025-08-26","refereed":"nonPeerReviewed","hostedBy":{"key":"doajarticles::55c591cd7491eb12cb76474ffa5ee51f","value":"Translational Psychiatry"},"collectedFrom":{"key":"opendoar____::8b6dd7db9af49e67306feb59a8bdc52c","value":"Europe PubMed Central"}},{"alternateIdentifiers":[{"scheme":"doi","value":"10.1038/s41398-025-03509-x"}],"license":"CC BY","accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":null},"type":"Article","urls":["https://pubmed.ncbi.nlm.nih.gov/40819083/","https://doi.org/10.1038/s41398-025-03509-x","https://pmc.ncbi.nlm.nih.gov/articles/PMC12357907/"],"publicationDate":"2025-08-16","refereed":"nonPeerReviewed","hostedBy":{"key":"opendoar____::eda80a3d5b344bc40f3bc04f65b7a357","value":"PubMed Central"},"collectedFrom":{"key":"opendoar____::eda80a3d5b344bc40f3bc04f65b7a357","value":"PubMed Central"}},{"pids":[{"scheme":"handle","value":"21.11116/0000-0011-B13C-2"},{"scheme":"handle","value":"21.11116/0000-0012-82A3-0"}],"alternateIdentifiers":[{"scheme":"doi","value":"10.1038/s41398-025-03509-x"}],"license":"CC BY","accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":null},"type":"Article","urls":["https://hdl.handle.net/21.11116/0000-0012-82A3-0","https://hdl.handle.net/21.11116/0000-0011-B13C-2"],"publicationDate":"2025-08-16","refereed":"nonPeerReviewed","hostedBy":{"key":"opendoar____::958adb57686c2fdec5796398de5f317a","value":"MPG.PuRe"},"collectedFrom":{"key":"opendoar____::958adb57686c2fdec5796398de5f317a","value":"MPG.PuRe"}},{"alternateIdentifiers":[{"scheme":"doi","value":"10.1038/s41398-025-03509-x"}],"license":"CC BY","accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":"gold"},"type":"Article","urls":["http://dx.doi.org/10.1038/s41398-025-03509-x"],"refereed":"nonPeerReviewed","hostedBy":{"key":"doajarticles::55c591cd7491eb12cb76474ffa5ee51f","value":"Translational Psychiatry"},"collectedFrom":{"key":"openaire____::a8db6f6b2ce4fe72e8b2314a9a93e7d9","value":"Sygma"}}],"links":[{"header":{"relationType":"resultProject","relationClass":"isProducedBy","relatedIdentifier":"corda_____he::b08a003ad24942a4266996265199b7ae","relatedRecordType":"project","relationProvenance":"sysimport:crosswalk","trust":"0.9"},"collectedfrom":[{"dsId":"openaire____::3f264f93cf3b0cfc4ede188a6300455c","dsName":"CORDA - COmmon Research DAta Warehouse - Horizon Europe"}],"projectTitle":"Psych-STRATA - A Stratified Treatment Algorithm in Psychiatry: A program on stratified pharmacogenomics in severe mental illness","code":"101057454","funding":{"funder":{"id":"ec__________::EC","shortname":"EC","name":"European Commission","jurisdiction":{"code":"EU","label":"European Union"},"pid":null},"level0":{"id":"ec__________::EC::HE","description":"Horizon Europe Framework Programme","name":"HE"},"level1":{"id":"ec__________::EC::HE::HORIZON-RIA","description":"HORIZON  Research and Innovation Actions","name":"HORIZON-RIA"},"level2":{"id":null,"description":null,"name":null}},"startDate":"2022-10-01","endDate":"2027-09-30"},{"header":{"relationType":"resultProject","relationClass":"isProducedBy","relatedIdentifier":"corda_____he::6c34a6f838e437b7092850942dfb9e07","relatedRecordType":"project","relationProvenance":"sysimport:crosswalk","trust":"0.9"},"collectedfrom":[{"dsId":"openaire____::3f264f93cf3b0cfc4ede188a6300455c","dsName":"CORDA - COmmon Research DAta Warehouse - Horizon Europe"}],"projectTitle":"Enabling Decentralised Digital Twin Era in existing Research Infrastructures for Predictive, Preventive, Personalised, and Participatory Health","code":"101188432","funding":{"funder":{"id":"ec__________::EC","shortname":"EC","name":"European Commission","jurisdiction":{"code":"EU","label":"European Union"},"pid":null},"level0":{"id":"ec__________::EC::HE","description":"Horizon Europe Framework Programme","name":"HE"},"level1":{"id":"ec__________::EC::HE::HORIZON-RIA","description":"HORIZON  Research and Innovation Actions","name":"HORIZON-RIA"},"level2":{"id":null,"description":null,"name":null}},"startDate":"2025-01-01","endDate":"2028-12-31"}],"otherTitles":null,"inDiamondJournal":false,"green":true,"isGreen":true,"isInDiamondJournal":false}