miR-195/497 induce postnatal quiescence of skeletal muscle stem cells
miR-195/497 induce postnatal quiescence of skeletal muscle stem cells
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DOI：
10.1038/ncomms5597
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发表时间：
2014-08-01
影响因子：
16.6
通讯作者：
Sehara-Fujisawa, Atsuko
中科院分区：
文献类型：
--
作者：
Sato, Takahiko;Yamamoto, Takuya;Sehara-Fujisawa, Atsuko
骨骼肌干细胞（MuSCs）是脊椎动物骨骼肌再生的主要来源，在成人骨骼肌中处于细胞周期阻滞状态。先前的证据表明，胚胎肌祖细胞增殖并分化形成肌纤维并自我更新，这意味着来源于这些细胞的musc在发育后期获得静止。在成年musc中，Dicer的消耗促进了它们从静止状态中退出，这表明microrna参与了静止状态的维持。在这里，我们发现miR-195和miR-497通过靶向细胞周期基因Cdc25和Ccnd诱导细胞周期阻滞。由于miR-195/497过表达或Cdc25/Ccnd减弱，幼龄musc中MyoD的表达降低，揭示了musc中静止和肌肉发生抑制之间的密切联系。用miR-195/497处理培养的musc移植有助于更有效地再生肌营养不良蛋白缺陷小鼠的肌肉，这表明miR-195/497在干细胞治疗中的潜在用途。
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.