Adult muscle stem cells, or satellite cells, ensure muscle regeneration and are embedded in a niche that contains myofibres and extracellular matrix (ECM). Bonaldo and colleagues used a mouse model lacking the collagen VI protein to demonstrate that the ECM modulates myofibre stiffness to ensure optimal activity of the satellite cells (Nat. Commun. 4, 1964; 2013).

The authors observed that collagen VI is expressed by satellite cells and deposited in the interstitial ECM in muscle, and found that its expression is induced by injury. They described a decrease in satellite cell numbers after injury as well as impaired satellite cell activity and muscle regeneration in the collagen VI knockout mice. In vitro, these mutant satellite cells were not able to differentiate to cardiomyocytes, and displayed poor survival properties. The authors also demonstrate that collagen-VI-deficient satellite cells transplanted alongside wild-type satellite cells, or fibroblasts (which can produce collagen VI), show restored regeneration capacity. It is known that physiological levels of muscle stiffness are required for optimal differentiation of stem cells into myoblasts. Mechanistically, the authors found that muscle isolated from the collagen VI knockout mice has lower stiffness properties than wild-type fibres following injury, and that growing wild-type satellite cells on these mutant fibres or transplanting these cells in a mutant animal decreases their regeneration properties.