The aged niche disrupts muscle stem cell quiescence.
The aged niche disrupts muscle stem cell quiescence.
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DOI：
10.1038/nature11438
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发表时间：
2012-10-18
期刊：
影响因子：
64.8
通讯作者：
Brack AS
中科院分区：
文献类型：
--
作者：
Chakkalakal JV;Jones KM;Basson MA;Brack AS
小生境是干细胞静止和功能的保守调节因子。在衰老过程中，干细胞功能下降。生态位内与年龄有关的变化在多大程度上和以何种方式促成了这一现象尚不清楚。我们证明，老年肌肉干细胞龛，肌肉纤维，表达FGF2在稳态条件下，驱动卫星细胞的一个子集打破静止，失去自我更新能力。我们发现，相对休眠的老年卫星细胞强烈表达Sprouty1（SPRY 1），FGF信号传导的抑制剂。在稳态条件下，通过去除spry 1增加衰老卫星细胞中的FGF信号传导，导致静止丧失、卫星细胞耗竭和再生能力降低。相反，通过抑制FGFR1信号传导或卫星细胞中spry 1的过表达来降低小生境衍生的FGF活性可防止其耗竭。这些实验确定了干细胞生态位中直接影响干细胞静止和功能的年龄依赖性变化。
The niche is a conserved regulator of stem cell quiescence and function. During aging, stem cell function declines. To what extent and by which means age-related changes within the niche contribute to this phenomenon are unknown. We demonstrate that the aged muscle stem cell niche, the muscle fiber, expresses FGF2 under homeostatic conditions, driving a subset of satellite cells to break quiescence and lose self-renewing capacity. We show that relatively dormant aged satellite cells robustly express Sprouty1 (spry1), an inhibitor of FGF signalling. Increasing FGF signalling in aged satellite cells under homeostatic conditions by removing spry1, results in the loss of quiescence, satellite cell depletion and diminished regenerative capacity. Conversely, reducing niche-derived FGF activity through inhibition of FGFR1 signalling or overexpression of spry1 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.
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