Muscle Satellite Cells Are Primed for Myogenesis but Maintain Quiescence with Sequestration of Myf5 mRNA Targeted by microRNA-31 in mRNP Granules
Muscle Satellite Cells Are Primed for Myogenesis but Maintain Quiescence with Sequestration of Myf5 mRNA Targeted by microRNA-31 in mRNP Granules
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DOI：
10.1016/j.stem.2012.03.011
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发表时间：
2012-07-06
期刊：
影响因子：
23.9
通讯作者：
Buckingham, Margaret
中科院分区：
文献类型：
--
作者：
Crist, Colin G.;Montarras, Didier;Buckingham, Margaret
成体组织的再生依赖于干细胞，这些干细胞已经准备好进入分化程序，同时保持静止。骨骼肌是如何协调这两个特征的，在骨骼肌中，大多数静止的卫星细胞转录成肌决定基因Myf5，而不激活成肌程序。我们发现Myf5 mRNA和调节其翻译的microRNA-31一起隔离在静止的卫星细胞中的mRNP颗粒中。在激活的卫星细胞中，mRNP颗粒解离，miR-31的相对水平降低，Myf5蛋白积累，这最初需要翻译，但不需要转录。促进mRNP颗粒持续存在的条件推迟了肌肉发生的开始。对miR-31水平的调控会影响卫星细胞的体外分化和体内肌肉再生。因此，我们提出了一个模型，在该模型中，转录后机制保持静止的干细胞准备进入组织特异性分化程序。
Regeneration of adult tissues depends on stem cells that are primed to enter a differentiation program, while remaining quiescent. How these two characteristics can be reconciled is exemplified by skeletal muscle in which the majority of quiescent satellite cells transcribe the myogenic determination gene Myf5, without activating the myogenic program. We show that Myf5 mRNA, together with microRNA-31, which regulates its translation, is sequestered in mRNP granules present in the quiescent satellite cell. In activated satellite cells, mRNP granules are dissociated, relative levels of miR-31 are reduced, and Myf5 protein accumulates, which initially requires translation, but not transcription. Conditions that promote the continued presence of mRNP granules delay the onset of myogenesis. Manipulation of miR-31 levels affects satellite cell differentiation ex vivo and muscle regeneration in vivo. We therefore propose a model in which posttranscriptional mechanisms hold quiescent stem cells poised to enter a tissue-specific differentiation program.