Muscle Stem Cells Exhibit Distinct Clonal Dynamics in Response to Tissue Repair and Homeostatic Aging.
Muscle Stem Cells Exhibit Distinct Clonal Dynamics in Response to Tissue Repair and Homeostatic Aging.
复制标题
肌肉干细胞在响应组织修复和稳态衰老时表现出独特的克隆动力学。
DOI：
10.1016/j.stem.2017.11.009
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发表时间：
2018
期刊：
影响因子：
23.9
通讯作者：
Sacco,Alessandra
中科院分区：
文献类型：
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作者：
Tierney,MatthewT;Stec,MichaelJ;Rulands,Steffen;Simons,BenjaminD;Sacco,Alessandra
成体干细胞库的克隆复杂性在几种组织的稳态周转过程中逐渐丧失，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库的功能影响，以及不同的组织微环境如何有助于这种减少，目前还知之甚少。在这里，我们进行了骨骼肌干细胞（MuSC）的克隆性细胞谱系追踪，以解决这些问题。我们发现，尽管增殖能力异源性降低，但MuSC克隆的复杂性在衰老过程中得以维持，这使得老年肌肉能够对损伤产生克隆多样性，尽管这种多样性有所减弱。相比之下，组织修复的反复发作导致指示中性漂移的MuSC克隆复杂性的进行性降低。一致地，生物统计学建模表明，MuSC在组织修复期间经历对称扩增和随机命运获取。这些发现建立了在稳态老化和肌肉再生过程中干细胞动力学的独特原则。
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.