Evidence map›Paper›PMID 40819083›Full record

ArticleTranslational psychiatry2025

iPSC-modelling reveals genetic associations and morphological alterations of oligodendrocytes in schizophrenia.

Man-Hsin Chang, Jan Benedikt Waldeck, Marius Stephan, Nirmal Kannaiyan, Valéria de Almeida, Emanuel Boudriot, Temmuz Karali, Lukas Röll, Laura Fischer, Damianos Demetriou and 8 more

Abstract read
In one paragraph

Article in Translational psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Man-Hsin Chang *Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0009-0009-4939-2547
Jan Benedikt Waldeck *Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0009-0001-5225-9933
Marius StephanDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0000-0003-1889-3049
Nirmal KannaiyanDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0000-0002-7408-6842
Valéria de AlmeidaDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.
Emanuel BoudriotDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0000-0001-6083-6318
Temmuz KaraliDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.
Lukas RöllDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0000-0002-0284-2290
Laura FischerMax Planck Institute of Psychiatry, 80804, Munich, Germany.ORCID http://orcid.org/0000-0001-8752-5827
Damianos DemetriouDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.
Nadia GabelliniDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.
Sabrina GalinskiDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.
Andrea SchmittDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0000-0002-5426-4023
Sergi PapiolMax Planck Institute of Psychiatry, 80804, Munich, Germany.ORCID http://orcid.org/0000-0001-9366-8728
Daniel KeeserDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0000-0002-0244-1024
Peter FalkaiDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany.ORCID http://orcid.org/0000-0003-2873-8667
Moritz J RossnerDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany. moritz.rossner@med.uni-muenchen.de.ORCID http://orcid.org/0000-0002-0667-3420
Florian J RaabeDepartment of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, 80336, Munich, Germany. florian_raabe@psych.mpg.de.ORCID http://orcid.org/0000-0001-8538-0783

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Induced Pluripotent Stem CellsOligodendrogliaSchizophreniaAdultDiffusion Tensor ImagingFemaleHumansMaleMiddle AgedWhite Matter

Identifiers

PMID40819083
PMCPMC12357907

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.