Core Transcription Factors Promote Induction of PAX3-Positive Skeletal Muscle Stem Cells

Takahiko Sato, Koki Higashioka, Hidetoshi Sakurai, Takuya Yamamoto, N. Goshima, M. Ueno, Chie Sotozono

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The use of adult skeletal muscle stem cells (MuSCs) for cell therapy has been attempted for decades, but still encounters considerable difficulties. MuSCs derived from human induced pluripotent stem cells (hiPSCs) are promising candidates for stem cell therapy to treat Duchenne muscular dystrophy (DMD). Here we report that four transcription factors, HEYL, KLF4, MYOD, and PAX3, selected by comprehensive screening of different MuSC populations, enhance the derivation of PAX3-positive myogenic progenitors from fibroblasts and hiPSCs, using medium that promotes the formation of presomitic mesoderm. These induced PAX3-positive cells contribute efficiently to the repair of DMD-damaged myofibers and also reconstitute the MuSC population. These studies demonstrate how a combination of core transcription factors can fine-tune the derivation of MuSCs capable of contributing to the repair of adult skeletal muscle. In this article, Sato and colleagues show that four transcription factors, Heyl, Klf4, MyoD, and Pax3, selected by comprehensive screening of mouse muscle stem cells, enhance the derivation of PAX3-positive myogenic progenitors from fibroblasts and hiPSCs. These induced PAX3-positive cells contribute efficiently to the repair of DMD-damaged myofibers and also reconstitute stem cell population.

Original languageEnglish
Pages (from-to)352-365
Number of pages14
JournalStem Cell Reports
Volume13
Issue number2
DOIs
Publication statusPublished - 13-08-2019

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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    Sato, T., Higashioka, K., Sakurai, H., Yamamoto, T., Goshima, N., Ueno, M., & Sotozono, C. (2019). Core Transcription Factors Promote Induction of PAX3-Positive Skeletal Muscle Stem Cells. Stem Cell Reports, 13(2), 352-365. https://doi.org/10.1016/j.stemcr.2019.06.006