摘要
Adult skeletal muscle stem cells,also known satellite cells(SCs),are a highly heterogeneous population and reside between the basal lamina and the muscle fiber sarcolemma.Myofibers function as an immediate niche to support SC self-renewal and activation during muscle growth and regeneration.Herein,we demonstrate that microRNA 378(miR-378)regulates glycolytic metabolism in skeletal muscle fibers,as evidenced by analysis of myofiber-specific miR-378 transgenic mice(TG).Subsequently,we evaluate SC function and muscle regeneration using miR-378 TG mice.We demonstrate that miR-378 TG mice significantly attenuate muscle regeneration because of the delayed activation and differentiation of SCs.Furthermore,we show that the miR-378-mediated metabolic switch enriches Pax7^(Hi) SCs,accounting for impaired muscle regeneration in miR-378 TG mice.Mechanistically,our data suggest that miR-378 targets the Akt1/FoxO1 pathway,which contributes the enrichment of Pax7^(Hi) SCs in miR-378 TG mice.Together,our findings indicate that miR-378 is a target that links fiber metabolism to muscle stem cell heterogeneity and provide a genetic model to approve the metabolic niche role of myofibers in regulating muscle stem cell behavior and function.
基金
This work was supported by grants from the National Natural Science Foundation of China(91949106,31971080 and 32000603)
the Natural Science Foundation of Beijing(7192125).
