Abstract:
:Organoid techniques provide unique platforms to model brain development and neurological disorders. Whereas several methods for recapitulating corticogenesis have been described, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, has been lacking until recently. Here, we describe the generation of MGE and cortex-specific organoids from human pluripotent stem cells that recapitulate the development of MGE and cortex domains, respectively. Population and single-cell RNA sequencing (RNA-seq) profiling combined with bulk assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analyses revealed transcriptional and chromatin accessibility dynamics and lineage relationships during MGE and cortical organoid development. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, fusing region-specific organoids followed by live imaging enabled analysis of human interneuron migration and integration. Together, our study provides a platform for generating domain-specific brain organoids and modeling human interneuron migration and offers deeper insight into molecular dynamics during human brain development.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Xiang Y,Tanaka Y,Patterson B,Kang YJ,Govindaiah G,Roselaar N,Cakir B,Kim KY,Lombroso AP,Hwang SM,Zhong M,Stanley EG,Elefanty AG,Naegele JR,Lee SH,Weissman SM,Park IHdoi
10.1016/j.stem.2017.07.007subject
Has Abstractpub_date
2017-09-07 00:00:00pages
383-398.e7issue
3eissn
1934-5909issn
1875-9777pii
S1934-5909(17)30286-2journal_volume
21pub_type
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