We systematically mapped how morphogen timing and dosage shape early cell fate specification in human neural organoids to unify our understanding of neural regionalization and to accelerate development of organoid models. This defined competence windows for key signaling pathways and benchmarked variability across human pluripotent stem cell lines and protocols.
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References
Kiecker, C. & Lumsden, A. The role of organizers in patterning the nervous system. Annu. Rev. Neurosci. 35, 347–367 (2012). A review article that presents how signaling factors such as morphogens shape the developing nervous system.
Stoeckius, M. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat. Methods 14, 865–868 (2017). This paper reports a multiplexed method combining single-cell transcriptomics with sample barcoding (epitope profiling using oligo-tagged antibodies).
Amin, N. D. et al. Generating human neural diversity with a multiplexed morphogen screen in organoids. Cell Stem Cell 31, 1831–1846.e9 (2024). This paper reports a morphogen screen in neural organoids mapping cell diversity after more than two months of differentiation.
Azbukina, N. et al. Multi-omic human neural organoid cell atlas of the posterior brain. Preprint at bioRxiv https://doi.org/10.1101/2025.03.20.644368 (2025). This paper reports a morphogen screen expanding the diversity of posterior brain regions in neural organoids.
Klein, D. et al. CellFlow enables generative single-cell phenotype modeling with flow matching. Preprint at bioRxiv https://doi.org/10.1101/2025.04.11.648220 (2025). This paper reports a framework for modeling developmental perturbations, including neural organoids.
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This is a summary of: Sanchís-Calleja, F. et al. Systematic scRNA-seq screens profile neural organoid response to morphogens. Nat. Methods https://doi.org/10.1038/s41592-025-02927-5 (2025).
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Dissecting how morphogens shape cell fates in human neural organoids. Nat Methods (2025). https://doi.org/10.1038/s41592-025-02959-x
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DOI: https://doi.org/10.1038/s41592-025-02959-x
