Individual brain organoids reproducibly form cell diversity of the human cerebral cortex
Name
nihms-1529307.pdf
Description
Accepted version
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4.39 MB
Format
Adobe PDF
Checksum (MD5)
af3588e53edb94c870eb2b01c368e9a2
Author(s)
Regev, Aviv
Date Issued
June 2019
Journal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Velasco, Silvia et al. “Individual brain organoids reproducibly form cell diversity of the human cerebral cortex.” Nature 570 (2019): 523-527 © 2019 The Author(s)
Version
Author's final manuscript
Abstract
Experimental models of the human brain are needed for basic understanding of its development and disease1. Human brain organoids hold unprecedented promise for this purpose; however, they are plagued by high organoid-to-organoid variability2,3. This has raised doubts as to whether developmental processes of the human brain can occur outside the context of embryogenesis with a degree of reproducibility that is comparable to the endogenous tissue. Here we show that an organoid model of the dorsal forebrain can reliably generate a rich diversity of cell types appropriate for the human cerebral cortex. We performed single-cell RNA-sequencing analysis of 166,242 cells isolated from 21 individual organoids, finding that 95% of the organoids generate a virtually indistinguishable compendium of cell types, following similar developmental trajectories and with a degree of organoid-to-organoid variability comparable to that of individual endogenous brains. Furthermore, organoids derived from different stem cell lines show consistent reproducibility in the cell types produced. The data demonstrate that reproducible development of the complex cellular diversity of the central nervous system does not require the context of the embryo, and that establishment of terminal cell identity is a highly constrained process that can emerge from diverse stem cell origins and growth environments.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/S41586-019-1289-X
