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Transcriptional landscape of human myogenesis reavels a key role of TWIST1 in maintenance of skeletal muscle progenitors

ABSTRACT: Derivation of human skeletal muscle in vitro with human pluripotent stem cells (hPSCs) opens new avenues for deciphering essential, but poorly understood aspects of transcriptional regulation in myogenic specification and relevance to rare genetic diseases. We characterized the transcriptional landscape of distinct human myogenic stages, including OCT4::EGFP+ PSCs, MSGN1::EGFP+ presomites, PAX7::EGFP+ skeletal muscle progenitors, MYOG::EGFP+ myoblasts, and multinucleated myotubes. We defined signature gene expression profiles from each population with unbiased clustering analysis, which provided unique insights into the transcriptional dynamics of human myogenesis from undifferentiated hPSCs to fully differentiated myotubes. Using knock-out strategy, we identified TWIST1 as a critical factor in maintenance of human PAX7::EGFP+ putative skeletal muscle progenitors, providing an explanation for the musculoskeletal symptoms of a rare genetic disease, Saethre-Chotzen syndrome. We have established a foundation for future studies to identify regulators of human myogenic ontogeny.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129505 | GEO | 2019/04/10

REPOSITORIES: GEO

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