TY - JOUR
T1 - MiR-195/497 induce postnatal quiescence of skeletal muscle stem cells
AU - Sato, Takahiko
AU - Yamamoto, Takuya
AU - Sehara-Fujisawa, Atsuko
N1 - Funding Information:
We thank Margaret Buckingham and Didier Montarras for discussions and careful reading of the manuscript. This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the project for realization of regenerative medicine (T.S. and A.S.-F.), a grant for Nervous and Mental Disorders from the Ministry of Health, Labour, and Welfare (A.S.-F.), molecular mechanisms underlying reconstruction of 3D structures during regeneration (T.S.), a grant from Takeda Science Foundation (T.S.), a grant from Uehara Memorial Foundation (T.S.). A part of this work was also supported by the Center for Frontier Medicine of the Kyoto University Global COE Program and Platform for Dynamic Approaches to Living System from the Ministry of Education, Culture, Sports, Science and Technology, Japan (T.S and A.S.-F.).
PY - 2014/8/14
Y1 - 2014/8/14
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms5597
DO - 10.1038/ncomms5597
M3 - Article
C2 - 25119651
AN - SCOPUS:84907305032
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 4597
ER -