Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors
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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DOI：
10.7554/elife.46981
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发表时间：
2020-02-03
期刊：
影响因子：
7.7
通讯作者：
Lee, Gabsang
中科院分区：
文献类型：
--
作者：
Choi, In Young;Lim, Hotae;Lee, Gabsang
用人类多能干细胞（hPSC）生成骨骼肌细胞，为破译人类肌原性规范中转录调控的基本但知之甚少的方面开辟了新途径。在这项研究中，我们描述了不同人类肌生成阶段的转录景观，包括 OCT4::EGFP+ 多能干细胞、MSGN1::EGFP+ 前体细胞、PAX7::EGFP+ 骨骼肌祖细胞、MYOG::EGFP+ 成肌细胞和多核肌管。我们通过无偏聚类分析定义了每个分离细胞群的特征基因表达谱，这为从未分化的 hPSC 到完全分化的肌管的人类肌生成的转录动力学提供了独特的见解。使用敲除策略，我们确定 TWIST1 是维持人类 PAX7::EGFP+ 假定骨骼肌祖细胞的关键因素。我们的数据揭示了 TWIST1 在人类骨骼肌祖细胞中的新作用，并且我们已经为识别人类肌源性个体发育的转录调控奠定了基础。
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.