Fusion of regionally-specified hPSC-derived organoids models human brain development and interneuron migration
By Yangfei Xiang, Yoshiaki Tanaka, Benjamin Patterson, Young‐Jin Kang, G. Govindaiah, N. Roselaar, Bilal Cakir, Kun-Yong Kim, A. Lombroso, Sung-Min Hwang and 7 more. Cell Stem Cell, 2017
613 citations recorded by the source corpus.
Summary Organoid techniques provide unique platforms to model brain development and neurological disorders. While 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-seq profiling combined with bulk 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, for modeling human interneuron migration, and offers deeper insight into molecular dynamics during human brain development.
Subfields: Developmental Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/475dd7a1415583e582c9a267294fb1a9cd62eae0
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Citations in the corpus
- Brain organoids: advances, applications and challenges (2019, background): “…(TH)-positive dopaminergic neurons, when combined with pharmacological treatment to induce neurodegeneration, may potentially serve as a relevant model for Parkinson’s disease and a cellular source for cell-replacement therapies (Monzel et al., 2017; Qian et al., 2016; Xiao et al., 2016).”