Self-organized developmental patterning and differentiation in cerebral organoids

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Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia. Consistent with this, we demonstrate the presence of forebrain organizing centers that express secreted growth factors, which may be involved in dorso-ventral patterning within organoids. Furthermore, we demonstrate the timed generation of neurons with mature morphologies, as well as the subsequent generation of astrocytes and oligodendrocytes. Our work provides the methodology and quality criteria for phenotypic analysis of brain organoids and shows that the spatial and temporal patterning events governing human brain development can be recapitulated in vitro.
Publisher
WILEY
Issue Date
2017-05
Language
English
Article Type
Article
Citation

EMBO JOURNAL, v.36, no.10, pp.1316 - 1329

ISSN
0261-4189
DOI
10.15252/embj.201694700
URI
http://hdl.handle.net/10203/264049
Appears in Collection
MSE-Journal Papers(저널논문)
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