Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration.
Cell Stem Cell, 2017/09/07;21(3):383-398.e7.
Xiang Y[1], Tanaka Y[1], Patterson B[1], Kang YJ[2], Govindaiah G[2], Roselaar N[1], Cakir B[1], Kim KY[1], Lombroso AP[3], Hwang SM[1], Zhong M[4], Stanley EG[5], Elefanty AG[5], Naegele JR[3], Lee SH[2], Weissman SM[1], Park IH[6]
Affiliations
PMID: 28757360DOI: 10.1016/j.stem.2017.07.007
Impact factor: 25.269
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.
Keywords: ATAC-seq; MGE; brain organoid; cortex; fusion; hESC; interneuron; neuronal migration; single cell RNA-seq; transcriptional regulation
MeSH terms
Brain; Cell Differentiation; Cell Lineage; Cell Movement; Cerebral Cortex; Chromatin; Humans; Interneurons; Median Eminence; Models, Biological; Organoids; Pluripotent Stem Cells; Sequence Analysis, RNA; Transcriptome
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