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Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors
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Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors
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Journal Article
Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors
2020
Overview
Generation of skeletal muscle cells with human pluripotent stem cells (hPSCs) opens new avenues for deciphering essential, but poorly understood aspects of transcriptional regulation in human myogenic specification. In this study, we characterized the transcriptional landscape of distinct human myogenic stages, including OCT4::EGFP+ pluripotent stem cells, MSGN1::EGFP+ presomite cells, PAX7::EGFP+ skeletal muscle progenitor cells, MYOG::EGFP+ myoblasts, and multinucleated myotubes. We defined signature gene expression profiles from each isolated cell population with unbiased clustering analysis, which provided unique insights into the transcriptional dynamics of human myogenesis from undifferentiated hPSCs to fully differentiated myotubes. Using a knock-out strategy, we identified TWIST1 as a critical factor in maintenance of human PAX7::EGFP+ putative skeletal muscle progenitor cells. Our data revealed a new role of TWIST1 in human skeletal muscle progenitors, and we have established a foundation to identify transcriptional regulations of human myogenic ontogeny (online database can be accessed in http://www.myogenesis.net/).
Publisher
eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
/ CRISPR
/ Gene Expression Regulation, Developmental - genetics
/ Humans
/ Muscle Development - genetics
/ Muscle Fibers, Skeletal - metabolism
/ Myotubes
/ Nuclear Proteins - metabolism
/ Ontogeny
/ Pluripotent Stem Cells - metabolism
/ Roles
/ Stem Cells and Regenerative Medicine
/ Twist-Related Protein 1 - genetics
/ Twist-Related Protein 1 - metabolism
/ TWIST1
