Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration.
Cell Stem Cell
; 21(3): 383-398.e7, 2017 09 07.
Article
en En
| MEDLINE
| ID: mdl-28757360
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Organoides
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Movimiento Celular
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Células Madre Pluripotentes
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Interneuronas
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Modelos Biológicos
Límite:
Humans
Idioma:
En
Revista:
Cell Stem Cell
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos