title: miR-195/497 induce postnatal quiescence of skeletal muscle stem cells.
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.
authors.affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sato
authors.affiliation: 1] Center for iPS Cell Research and Application, Department of Reprogramming Science, Kyoto University, Kyoto 606-8507, Japan [2] Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sehara-Fujisawa
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D035683:MicroRNAs / Q000502:physiology*; D009024:Morphogenesis / Q000502:physiology; D024510:Muscle Development / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000254:growth & development* / Q000502:physiology; D017570:MyoD Protein / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000502:physiology
chemical_list: C569389:MIRN195a microRNA, mouse; D035683:MicroRNAs; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C550139:mirn497 microRNA, mouse; D020687:cdc25 Phosphatases