The aged niche disrupts muscle stem cell quiescence

摘要

干细胞维护的效率随年龄增长而下降，但尚不rn清楚干细胞小环境是否在这种下降中扮演一个rn角色。Andrew Brack及其同事报告，随着年龄rn增长，小鼠骨骼肌小环境会变得更加有利于有rn丝分裂(以使更多细胞发生有丝分裂和分化)，rn而让骨骼肌干细胞保持静态的能力则下降。这rn会导致干细胞自我更新的能力下降。FGF2是rn衰老的小环境中的一个关键促有丝分裂因子，rn尽管少量肌肉干细胞表达Spry1(FGF信号作用rn的一个抑制因子)，并在衰老的骨骼肌纤维中rn保持一定的静置状态。%The niche is a conserved regulator of stem cell quiescence and function. During ageing, stem cell function declines. To what extent and by what means age-related changes within the niche contribute to this phenomenon are unknown. Here we demonstrate that the aged muscle stem cell niche, the muscle fibre, expresses Fgf2 under homeostatic conditions, driving a subset of satellite cells to break quiescence and lose their self-renewing capacity. We show in mice that relatively dormant aged satellite cells robustly express sprouty 1 (Spry1), an inhibitor of fibroblast growth factor (FGF) signalling. Increasing FGF signalling in aged satellite cells under homeostatic conditions by removing Spryl results in the loss of quiescence, satellite cell depletion and diminished regenerative capacity. Conversely, reducing niche-derived FGF activity through inhibition of Fgfrl signalling or overexpression of Spryl in satellite cells prevents their depletion. These experiments identify an age-dependent change in the stem cell niche that directly influences stem cell quiescence and function.