PRMT7 Preserves Satellite Cell Regenerative Capacity
PRMT7 Preserves Satellite Cell Regenerative Capacity
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DOI：
10.1016/j.celrep.2016.01.022
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发表时间：
2016-02-16
期刊：
影响因子：
8.8
通讯作者：
Richard, Stephane
中科院分区：
文献类型：
--
作者：
Blanc, Romeo Sebastien;Vogel, Gillian;Richard, Stephane
骨骼肌的再生需要静止的肌肉干细胞(卫星细胞)的持续存在，这些干细胞在损伤后被激活。在这里，我们报告了全身蛋白精氨酸甲基转移酶PRMT7(-/-)成年小鼠和使用Pax7-CreERT2的卫星细胞中条件缺失PRMT7的小鼠都表现出卫星细胞功能的显著降低，导致肌肉损伤后再生能力的缺陷。我们发现PRMT7在激活的卫星细胞中优先表达，有趣的是，缺乏PRMT7的卫星细胞经历细胞周期停滞和细胞过早衰老。这些缺陷导致卫星细胞干细胞在损伤后再生肌肉和自我更新的能力较差。缺乏PRMT7的卫星细胞表达高水平的CDK抑制物p21CIP1和低水平的抑制物Dnmt3b。在PRMT7缺陷细胞中修复Dnmt3b可以挽救PRMT7介导的衰老。我们的发现将PRMT7定义为维持肌肉干细胞再生能力所需的Dnmt3b/p21轴的调节因子。
Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells), which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7(-/-) adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.