TY - JOUR
KW - Cell type diversity
KW - Gene expression analysis
KW - Neural patterning
KW - Stem-cell differentiation
AU - Silvia Velasco
AU - Amanda J. Kedaigle
AU - Sean K. Simmons
AU - Allison Nash
AU - Marina Rocha
AU - Giorgia Quadrato
AU - Bruna Paulsen
AU - Lan Nguyen
AU - Xian Adiconis
AU - Aviv Regev
AU - Joshua Z. Levin
AU - Paola Arlotta
AB - 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.
BT - Nature
DA - 2019-06
DO - 10.1038/s41586-019-1289-x
IS - 7762
LA - en
N2 - 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.
PY - 2019
SP - 523
EP - 527
T2 - Nature
TI - Individual brain organoids reproducibly form cell diversity of the human cerebral cortex
UR - https://www.nature.com/articles/s41586-019-1289-x
VL - 570
Y2 - 2026-08-26
SN - 1476-4687
ER -