Myf5 haploinsufficiency reveals distinct cell fate potentials for adult skeletal muscle stem cells
Myf5 haploinsufficiency reveals distinct cell fate potentials for adult skeletal muscle stem cells
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DOI：
10.1242/jcs.097006
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发表时间：
2012-04-01
影响因子：
4
通讯作者：
Tajbakhsh, Shahragim
中科院分区：
文献类型：
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作者：
Gayraud-Morel, Barbara;Chretien, Fabrice;Tajbakhsh, Shahragim
成年小鼠骨骼肌干细胞的命运受到关键转录因子的调节，包括决定基因 Myf5 和 Myod。 Myf5 在调节静止肌肉干细胞中的确切作用仍然难以捉摸。在这里，我们表明，大多数（但不是全部）静止卫星细胞表达 Myf5 蛋白，但表达水平不同，并且与野生型卫星细胞相比，常驻 Myf5 杂合肌肉干细胞更容易产生肌源性定型。然而矛盾的是，与野生型干细胞相比，Myf5杂合细胞异型移植到再生肌肉中会导致更高的自我更新能力，而肌纤维的再生能力却没有改变。相比之下，通过转录组分析，Pax7 单倍体不足并未显示出重大修改。这些观察结果通过揭示与 Myf5 单倍体不足相关的两种不同且相反的表型，提供了一种将 Myf5 水平与肌肉干细胞异质性和命运联系起来的机制。这些发现对于如何通过关键转录因子调节干细胞命运同时产生反应性异质细胞库具有重要意义。
Skeletal muscle stem cell fate in adult mice is regulated by crucial transcription factors, including the determination genes Myf5 and Myod. The precise role of Myf5 in regulating quiescent muscle stem cells has remained elusive. Here we show that most, but not all, quiescent satellite cells express Myf5 protein, but at varying levels, and that resident Myf5 heterozygous muscle stem cells are more primed for myogenic commitment compared with wild-type satellite cells. Paradoxically however, heterotypic transplantation of Myf5 heterozygous cells into regenerating muscles results in higher self-renewal capacity compared with wild-type stem cells, whereas myofibre regenerative capacity is not altered. By contrast, Pax7 haploinsufficiency does not show major modifications by transcriptome analysis. These observations provide a mechanism linking Myf5 levels to muscle stem cell heterogeneity and fate by exposing two distinct and opposing phenotypes associated with Myf5 haploinsufficiency. These findings have important implications for how stem cell fates can be modulated by crucial transcription factors while generating a pool of responsive heterogeneous cells.