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Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration

2017; Elsevier BV; Volume: 21; Issue: 3 Linguagem: Inglês

10.1016/j.stem.2017.07.007

1934-5909

Yangfei Xiang, Yoshiaki Tanaka, Benjamin Patterson, Young-Jin Kang, Gubbi Govindaiah, Naomi Roselaar, Bilal Çakır, Kun-Yong Kim, Adam Lombroso, Sung‐Min Hwang, Mei Zhong, Edouard G. Stanley, Andrew G. Elefanty, Janice R. Naegele, Sang‐Hun Lee, Sherman M. Weissman, In‐Hyun Park,

Neurogenesis and neuroplasticity mechanisms

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.