Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors.
In Young ChoiHotae LimHyeon Jin ChoYohan OhBin-Kuan ChouHao BaiLinzhao ChengYong Jun KimSangHwan HyunHyesoo KimJoo Heon ShinGabsang LeePublished in: eLife (2020)
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/).
Keyphrases
- pluripotent stem cells
- skeletal muscle
- endothelial cells
- insulin resistance
- stem cells
- type diabetes
- emergency department
- gene expression
- machine learning
- induced apoptosis
- transcription factor
- epithelial mesenchymal transition
- metabolic syndrome
- signaling pathway
- social media
- cell death
- cell proliferation
- health information
- rna seq
- optical coherence tomography
- diabetic retinopathy