First Author | Blanc RS | Year | 2016 |
Journal | Cell Rep | Volume | 14 |
Issue | 6 | Pages | 1528-1539 |
PubMed ID | 26854227 | Mgi Jnum | J:271361 |
Mgi Id | MGI:6281057 | Doi | 10.1016/j.celrep.2016.01.022 |
Citation | Blanc RS, et al. (2016) PRMT7 Preserves Satellite Cell Regenerative Capacity. Cell Rep 14(6):1528-1539 |
abstractText | 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. |