Muscle Stem Cells Exhibit Distinct Clonal Dynamics in Response to Tissue Repair and Homeostatic Aging

Publication date: Available online 14 December 2017
Source:Cell Stem Cell
Author(s): Matthew T. Tierney, Michael J. Stec, Steffen Rulands, Benjamin D. Simons, Alessandra Sacco
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.

Graphical abstract

Teaser

Tierney et al. use multicolor lineage tracing at clonal levels to demonstrate that the control of muscle stem cell asymmetry is context-dependent, coordinated by individual divisions with homeostatic turnover, and at the population level during tissue repair.


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