Individual brain organoids reproducibly form cell diversity of the human cerebral cortex
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 proc...
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/125050 |
| _version_ | 1826216022757081088 |
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| author | Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Regev, Aviv |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:41:04Z |
| format | Article |
| id | mit-1721.1/125050 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:41:04Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1250502022-10-03T07:36:15Z Individual brain organoids reproducibly form cell diversity of the human cerebral cortex Regev, Aviv Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT 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. 2020-05-06T15:28:41Z 2020-05-06T15:28:41Z 2019-06 2020-01-28T17:30:08Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 https://hdl.handle.net/1721.1/125050 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) en 10.1038/S41586-019-1289-X Nature 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. application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Regev, Aviv Individual brain organoids reproducibly form cell diversity of the human cerebral cortex |
| title | Individual brain organoids reproducibly form cell diversity of the human cerebral cortex |
| title_full | Individual brain organoids reproducibly form cell diversity of the human cerebral cortex |
| title_fullStr | Individual brain organoids reproducibly form cell diversity of the human cerebral cortex |
| title_full_unstemmed | Individual brain organoids reproducibly form cell diversity of the human cerebral cortex |
| title_short | Individual brain organoids reproducibly form cell diversity of the human cerebral cortex |
| title_sort | individual brain organoids reproducibly form cell diversity of the human cerebral cortex |
| url | https://hdl.handle.net/1721.1/125050 |
| work_keys_str_mv | AT regevaviv individualbrainorganoidsreproduciblyformcelldiversityofthehumancerebralcortex |