Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells

  • Tomohiko Akiyama
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Shunichi Wakabayashi
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Atsumi Soma
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Saeko Sato
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Yuhki Nakatake
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Mayumi Oda
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Miyako Murakami
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Miki Sakota
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Nana Chikazawa-Nohtomi
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Shigeru B. H. Ko
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Minoru S. H. Ko
    Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan

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<jats:p>Human pluripotent stem cells (hPSCs) have the capacity to differentiate into essentially all cell types in the body. Such differentiation can be directed to specific cell types by appropriate cell culture conditions or overexpressing lineage-defining transcription factors (TFs). Especially, for the activation of myogenic program, early studies have shown the effectiveness of enforced expression of TFs associated with myogenic differentiation, such as PAX7 and MYOD1. However, the efficiency of direct differentiation was rather low, most likely due to chromatin features unique to hPSCs, which hinder the access of TFs to genes involved in muscle differentiation. Indeed, recent studies have demonstrated that ectopic expression of epigenetic-modifying factors such as a histone demethylase and an ATP-dependent remodeling factor significantly enhances myogenic differentiation from hPSCs. In this article, we review the recent progress for in vitro generation of skeletal muscles from hPSCs through forced epigenetic and transcriptional manipulation.</jats:p>

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