PRMT7 Preserves Satellite Cell Regenerative Capacity

• Main Authors: Roméo Sébastien Blanc, Gillian Vogel, Taiping Chen, Colin Crist, Stéphane Richard
• Format: Article
• Language: English
• Published: Elsevier 2016-02-01
• Series: Cell Reports
• Subjects: PRMT7; muscle regeneration; senescence; aging; DNMT3b; p21CIP1; muscle stem cell
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124716000437

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.