Roméo Sébastien Blanc, Gillian Vogel, Taiping Chen, Colin Crist Stéphane Richard
Publication stage: In Press Corrected Proof
Open Access
DOI: http://dx.doi.org/10.1016/j.celrep.2016.01.022
Highlights
- •PRMT7 is required for muscle stem cell self-renewal and regenerative capacity in vivo
- •PRMT7 deletion causes senescence of activated muscle stem cells
- •This entry into senescence is associated with persistent expression of p21
Summary
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.