类有机物
背景(考古学)
人脑
电池类型
神经科学
干细胞
生物
细胞
大脑皮层
细胞生物学
遗传学
古生物学
作者
Silvia Velasco,Amanda J. Kedaigle,Sean Simmons,Allison Nash,Marina Monzani da Rocha,Giorgia Quadrato,Bruna Paulsen,Lan Nguyễn,Xian Adiconis,Aviv Regev,Joshua Z. Levin,Paola Arlotta
出处
期刊:Nature
[Springer Nature]
日期:2019-06-01
卷期号:570 (7762): 523-527
被引量:649
标识
DOI:10.1038/s41586-019-1289-x
摘要
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.
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