The clonal complexity of adult stem cell pools is progressively lost during homeostatic turnover in several tissues, suggesting a decrease in the number of stem cells with distinct clonal origins. The functional impact of reduced complexity on stem cell pools, and how different tissue microenvironments may contribute to such a reduction, are poorly understood. Here, we performed clonal multicolor lineage tracing of skeletal muscle stem cells (MuSCs) to address these questions. We found that MuSC clonal complexity is maintained during aging despite heterogenous reductions in proliferative capacity, allowing aged muscle to mount a clonally diverse, albeit diminished, response to injury. In contrast, repeated bouts of tissue repair cause a progressive reduction in MuSC clonal complexity indicative of neutral drift. Consistently, biostatistical modeling suggests that MuSCs undergo symmetric expansions with stochastic fate acquisition during tissue repair. These findings establish distinct principles that underlie stem cell dynamics during homeostatic aging and muscle regeneration.

中文翻译：

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肌肉干细胞在响应组织修复和稳态老化时表现出不同的克隆动力学。

成体干细胞库的克隆复杂性在几个组织的稳态更新过程中逐渐丧失，这表明具有不同克隆起源的干细胞数量减少。复杂性降低对干细胞池的功能影响，以及不同的组织微环境如何促成这种减少，目前尚不清楚。在这里，我们对骨骼肌干细胞 (MusCs) 进行了克隆多色谱系追踪，以解决这些问题。我们发现，尽管增殖能力异质性降低，但 MuSC 克隆的复杂性在衰老过程中得以保持，从而使衰老的肌肉能够对损伤产生克隆多样化的反应，尽管有所减少。相比之下，重复的组织修复会导致 MuSC 克隆复杂性逐渐降低，这表明中性漂移。始终如一，生物统计模型表明，MuSC 在组织修复过程中经历了对称扩张和随机命运获取。这些发现确立了在稳态老化和肌肉再生过程中构成干细胞动力学的独特原则。