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He, Z.* ; Dony, L. ; Fleck, J.S.* ; Szałata, A. ; Li, K. ; Slišković, I. ; Lin, H.C.* ; Santel, M.* ; Atamian, A.* ; Quadrato, G.* ; Sun, J.* ; Pașca, S.P.* ; Camp, J.G.* ; Theis, F.J. ; Treutlein, B.*

An integrated transcriptomic cell atlas of human neural organoids.

Nature 635, 690-698 (2024)

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Open Access Green: Postprint online available 05/2025

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Human neural organoids, generated from pluripotent stem cells in vitro, are useful tools to study human brain development, evolution and disease. However, it is unclear which parts of the human brain are covered by existing protocols, and it has been difficult to quantitatively assess organoid variation and fidelity. Here we integrate 36 single-cell transcriptomic datasets spanning 26 protocols into one integrated human neural organoid cell atlas totalling more than 1.7 million cells^1-26. Mapping to developing human brain references^27-30 shows primary cell types and states that have been generated in vitro, and estimates transcriptomic similarity between primary and organoid counterparts across protocols. We provide a programmatic interface to browse the atlas and query new datasets, and showcase the power of the atlas to annotate organoid cell types and evaluate new organoid protocols. Finally, we show that the atlas can be used as a diverse control cohort to annotate and compare organoid models of neural disease, identifying genes and pathways that may underlie pathological mechanisms with the neural models. The human neural organoid cell atlas will be useful to assess organoid fidelity, characterize perturbed and diseased states and facilitate protocol development.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Pluripotent Stem-cells; Cerebral Organoids; Brain-development; Generation; Diversity

ISSN (print) / ISBN 0028-0836

e-ISSN 1476-4687

Journal Nature

Quellenangaben Volume: 635, Issue: 8039, Pages: 690-698

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants Joachim Herz Foundation
Bavarian Ministry of Science and the Arts in the framework of the Bavarian Research Association ForInter (Interaction of Human Brain Cells)
Roche Institute for Human Biology
European Union (European Research Council (ERC)
Swiss National Science Foundation
BMBF-funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI)
German-American Fulbright Commission
Chan Zuckerberg Initiative DAF, an advised fund of the Silicon Valley Community Foundation