Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 1528-1539 |
Number of pages | 12 |
Journal | Cell Reports |
Volume | 14 |
Issue number | 6 |
DOIs | |
State | Published - Feb 16 2016 |
Keywords
- Aging
- DNMT3b
- Muscle regeneration
- Muscle stem cell
- P21CIP1
- PRMT7
- Senescence
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology