Yue Feng, Bi Pengpeng, Wang Chao, Li Jie, Liu Xiaoqi, Kuang Shihuan
Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Cell Rep. 2016 Nov 22;17(9):2340-2353. doi: 10.1016/j.celrep.2016.11.002.
Skeletal muscle stem cells (satellite cells [SCs]) are normally maintained in a quiescent (G) state. Muscle injury not only activates SCs locally, but also alerts SCs in distant uninjured muscles via circulating factors. The resulting G SCs are adapted to regenerative cues and regenerate injured muscles more efficiently, but whether they provide any long-term benefits to SCs is unknown. Here, we report that embryonic myogenic progenitors lacking the phosphatase and tensin homolog (Pten) exhibit enhanced proliferation and differentiation, resulting in muscle hypertrophy but fewer SCs in adult muscles. Interestingly, Pten null SCs are predominantly in the G state, even in the absence of an injury. The G SCs are deficient in self-renewal and subjected to accelerated depletion during regeneration and aging and fail to repair muscle injury in old mice. Our findings demonstrate a key requirement of Pten in G entry of SCs and provide functional evidence that prolonged G leads to stem cell depletion and regenerative failure.
骨骼肌干细胞（卫星细胞[SCs]）通常维持在静止（G）状态。肌肉损伤不仅会局部激活卫星细胞，还会通过循环因子使远处未受伤肌肉中的卫星细胞被激活。由此产生的G期卫星细胞适应再生信号，能更有效地再生受伤肌肉，但它们是否能为卫星细胞带来任何长期益处尚不清楚。在此，我们报告称，缺乏磷酸酶和张力蛋白同源物（Pten）的胚胎肌源性祖细胞表现出增殖和分化增强，导致肌肉肥大，但成年肌肉中的卫星细胞数量减少。有趣的是，即使在没有损伤的情况下，Pten基因缺失的卫星细胞也主要处于G期。这些G期卫星细胞自我更新能力不足，在再生和衰老过程中加速耗竭，无法修复老年小鼠的肌肉损伤。我们的研究结果证明了Pten在卫星细胞进入G期过程中的关键作用，并提供了功能证据，表明延长的G期会导致干细胞耗竭和再生失败。
