Myf5 expression during fetal myogenesis defines the developmental progenitors of adult satellite cells.
Myf5 expression during fetal myogenesis defines the developmental progenitors of adult satellite cells.
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DOI：
10.1016/j.ydbio.2013.04.021
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发表时间：
2013-07-15
影响因子：
2.7
通讯作者：
Rando, Thomas A.
中科院分区：
文献类型：
--
作者：
Biressi, Stefano;Bjornson, Christopher R. R.;Carlig, Poppy M. M.;Nishijo, Koichi;Keller, Charles;Rando, Thomas A.
Myf5是肌肉特异性决定基因中的一员，在骨骼肌发育中起着关键作用。虽然Myf5在胚胎和胎儿肌肉发生过程中的表达已经被广泛研究，但它在祖细胞中的表达最终将产生成体卫星细胞，即负责肌肉修复的干细胞，在很大程度上仍未被探索。为了研究这一方面，我们产生了一个在Myf5基因座上携带Creer编码序列的小鼠品系。在该菌株中，三苯氧胺诱导的Cre活性与内源性Myf5的表达平行。结合Myf5CreER和Cre报告基因，我们能够评估不同发育阶段表达Myf5的细胞对成人后肢肌肉卫星细胞池的贡献。虽然在胚胎晚期(~E12)肢芽中的Myf5+Ve祖细胞亚群中可以追溯到一些罕见的卫星细胞的起源，但在胎儿期(~E15)首次表达Myf5的细胞中出现了相当数量的卫星细胞。这些研究提供了直接证据，证明成体卫星细胞来自于在肌肉发生的胎儿阶段首次表达肌源性决定基因Myf5的祖细胞。
Myf5 is a member of the muscle-specific determination genes and plays a critical role in skeletal muscle development. Whereas the expression of Myf5 during embryonic and fetal myogenesis has been extensively studied, its expression in progenitors that will ultimately give rise to adult satellite cells, the stem cells responsible for muscle repair, is still largely unexplored. To investigate this aspect, we have generated a mouse strain carrying a CreER coding sequence in the Myf5 locus. In this strain, Tamoxifen-inducible Cre activity parallels endogenous Myf5 expression. Combining Myf5CreER and Cre reporter alleles, we were able to evaluate the contribution of cells expressing Myf5 at distinct developmental stages to the pool of satellite cells in adult hindlimb muscles. Although it was possible to trace back the origin of some rare satellite cells to a subpopulation of Myf5+ve progenitors in the limb buds at the late embryonic stage (~E12), a significant number of satellite cells arise from cells which expressed Myf5 for the first time at the fetal stage (~E15). These studies provide direct evidence that adult satellite cells derive from progenitors that first express the myogenic determination gene Myf5 during fetal stages of myogenesis.
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