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

肌肉 PGC-1α 通过重塑干细胞生态位来调节卫星细胞数量和增殖

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作者:Ivana Dinulovic, Regula Furrer, Markus Beer, Arnaud Ferry, Bettina Cardel, Christoph Handschin

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 γ coactivator 1α (PGC-1α) is a key regulator of oxidative metabolism and endurance training adaptation. However, a link between PGC-1α and SC behavior remains unexplored.

Conclusions

Taken together, PGC-1α indirectly affects SC plasticity in skeletal muscle and thereby might contribute to improved SC activation in exercise.

Methods

We have now studied SC function in a PGC-1α fiber-specific gain-of-function animal model.

Results

In surprising contrast to bona fide exercise, muscle-specific PGC-1α transgenic mice have lower SC numbers. Nevertheless, SCs from these mice have a higher propensity for activation and proliferation. Intriguingly, muscle PGC-1α 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-1α indirectly affects SC plasticity in skeletal muscle and thereby might contribute to improved SC activation in exercise.

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