MiR-195/497 induce postnatal quiescence of skeletal muscle stem cells

Takahiko Sato, Takuya Yamamoto, Atsuko Sehara-Fujisawa

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Skeletal muscle stem cells (MuSCs), the major source for skeletal muscle regeneration in vertebrates, are in a state of cell cycle arrest in adult skeletal muscles. Prior evidence suggests that embryonic muscle progenitors proliferate and differentiate to form myofibres and also self-renew, implying that MuSCs, derived from these cells, acquire quiescence later during development. Depletion of Dicer in adult MuSCs promoted their exit from quiescence, suggesting microRNAs are involved in the maintenance of quiescence. Here we identified miR-195 and miR-497 that induce cell cycle arrest by targeting cell cycle genes, Cdc25 and Ccnd. Reduced expression of MyoD in juvenile MuSCs, as a result of overexpressed miR-195/497 or attenuated Cdc25/Ccnd, revealed an intimate link between quiescence and suppression of myogenesis in MuSCs. Transplantation of cultured MuSCs treated with miR-195/497 contributed more efficiently to regenerating muscles of dystrophin-deficient mice, indicating the potential utility of miR-195/497 for stem cell therapies.

Original languageEnglish
Article number4597
JournalNature communications
Volume5
DOIs
Publication statusPublished - 14-08-2014

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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