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

Tierney, Matthew T.; Stec, Michael J.; Rulands, Steffen; Simons, Benjamin D.; Sacco, Alessandra

doi:10.1016/j.stem.2017.11.009

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

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Rulands, Steffen
Max Planck Institute for the Physics of Complex Systems, Max Planck Society;

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http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(17)30461-7
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Citation

Tierney, M. T., Stec, M. J., Rulands, S., Simons, B. D., & Sacco, A. (2018). Muscle Stem Cells Exhibit Distinct Clonal Dynamics in Response to Tissue Repair and Homeostatic Aging. Cell Stem Cell, 22(1), 119-127.e3. doi:10.1016/j.stem.2017.11.009.

Cite as: https://hdl.handle.net/21.11116/0000-0000-C8BF-8

Abstract

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.