Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors
In Young Choi,
Hotae Lim,
Hyeon Jin Cho,
Yohan Oh,
Bin-Kuan Chou,
Hao Bai,
Linzhao Cheng,
Yong Jun Kim,
SangHwan Hyun,
Hyesoo Kim,
Joo Heon Shin,
Gabsang Lee
Affiliations
In Young Choi
The Institute for Cell Engineering, Johns Hopkins University, School of Medicine, Baltimore, United States; Department of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea
Hotae Lim
The Institute for Cell Engineering, Johns Hopkins University, School of Medicine, Baltimore, United States; College of Veterinary Medicine, Chungbuk National University, Chungbuk, Republic of Korea
Hyeon Jin Cho
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States
The Institute for Cell Engineering, Johns Hopkins University, School of Medicine, Baltimore, United States; Division of Hematology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Hao Bai
The Institute for Cell Engineering, Johns Hopkins University, School of Medicine, Baltimore, United States; Division of Hematology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Linzhao Cheng
Division of Hematology, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, United States
Yong Jun Kim
Department of Pathololgy, College of Medicine, Kyung Hee University, Seoul, Republic of Korea
SangHwan Hyun
The Institute for Cell Engineering, Johns Hopkins University, School of Medicine, Baltimore, United States; College of Veterinary Medicine, Chungbuk National University, Chungbuk, Republic of Korea
The Institute for Cell Engineering, Johns Hopkins University, School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, United States
Joo Heon Shin
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States
The Institute for Cell Engineering, Johns Hopkins University, School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, United States; The Solomon H. Synder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, United States
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/).
