Muscle PGC-1α modulates satellite cell number and proliferation by remodeling the stem cell niche

Background: The myogenic capacity of satellite cells (SCs), adult muscle stem cells, is influenced by aging, exercise, and other factors. In skeletal muscle, the peroxisome proliferator-activated receptor. coactivator 1a (PGC-1 alpha) is a key regulator of oxidative metabolism and endurance training adaptation. However, a link between PGC-1 alpha and SC behavior remains unexplored. Methods: We have now studied SC function in a PGC-1 alpha fiber-specific gain-of-function animal model. Results: In surprising contrast to bona fide exercise, muscle-specific PGC-1 alpha transgenic mice have lower SC numbers. Nevertheless, SCs from these mice have a higher propensity for activation and proliferation. Intriguingly, muscle PGC-1 alpha triggers a remodeling of the SC niche by altering the extracellular matrix composition, including the levels of fibronectin, which affects the proliferative output of SCs. Conclusions: Taken together, PGC-1 alpha indirectly affects SC plasticity in skeletal muscle and thereby might contribute to improved SC activation in exercise.