期刊
CELL STEM CELL
卷 21, 期 3, 页码 383-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2017.07.007
关键词
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资金
- NIH [GM0099130-01, GM111667-01]
- CSCRF [12-SCB-YALE-11, 13-SCB-YALE-06]
- KRIBB/KRCF research initiative program [NAP-09-3]
- CTSA grant from the National Center for Advancing Translational Science (NCATS), a component of the NIH [UL1 RR025750]
- NIH roadmap for Medical Research
- College of Medicine, University of Arkansas for Medical Sciences
- Core Facilities of the Center for Translational Neuroscience from the IDeA program at NIGMS [P30GM110702]
- NHMRC [GNT1117596, GNT1079004]
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 inter-neurons 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 (ATACseq) 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.
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