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Boerstler, T.* ; Kachkin, D.* ; Gerasimova, E.* ; Zagha, N.* ; Furlanetto, F.* ; Nayebzade, N.* ; Zappia, L. ; Boisvert, M. ; Farrell, M.* ; Ploetz, S.* ; Prots, I.* ; Regensburger, M.* ; Günther, C.* ; Winkler, J.* ; Gupta, P.* ; Theis, F.J. ; Karow, M.* ; Falk, S.* ; Winner, B.* ; Krach, F.*

Deciphering brain organoid heterogeneity by identifying key quality determinants.

Comm. Biol. 8:1412 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Brain organoids derived from human pluripotent stem cells (hPSCs) hold immense potential for modeling neurodevelopmental processes and disorders. However, their experimental variability and undefined organoid selection criteria for analysis hinder reproducibility. As part of the Bavarian ForInter consortium, we generated 72 brain organoids from distinct hPSC lines. We conducted a comprehensive analysis of their morphological and cellular characteristics at an early stage of their development. In our assessment, the Feret diameter emerged as a reliable, single parameter that characterizes brain organoid quality. Transcriptomic analysis of our organoid identified the abundance of unintended mesodermal differentiation as a major confounder of unguided brain organoid differentiation, correlating with Feret diameter. High-quality organoids consistently displayed a lower presence of mesenchymal cells. These findings provide a framework for enhancing brain organoid standardization and reproducibility, underscoring the need for morphological quality controls and considering the influence of mesenchymal cells on organoid-based modeling.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cerebral Organoids; Cell Diversity; Stem-cells; Models
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2399-3642
e-ISSN 2399-3642
Journal Communications Biology
Quellenangaben Volume: 8, Issue: 1, Pages: , Article Number: 1412 Supplement: ,
Publisher Springer
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503800-001
Grants Interdisziplinaeres Zentrum fur Klinische Forschung (IZKF) (Erstantragsteller project)
Bavarian Research Consortium 'Interaction of Human Brain Cells' (ForInter) network
Else Kroener-Fresenius-Stiftung
German Research Foundation
DFG
TreatHSP consortium (BMBF)
Bavarian Ministry of Science
DOI 10.1038/s42003-025-08855-6
WOS ID 001585289800002
Scopus ID 105017785251
PubMed ID 41034331
Erfassungsdatum 2025-11-06
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