Cited by 92Muscle Physiology and DisordersDevelopmental Biology and Gene RegulationMesenchymal stem cell research

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

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Tierney, Matthew T., Stec, Michael J., Rulands, Steffen, Simons, Benjamin D., Sacco, Alessandra·2018·Cell Stem Cell

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.

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Crossref · 10.1016/j.stem.2017.11.009

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  • In muscle, clonal expansion of MuSCs has been reported during tissue regeneration in response to acute injury, but has not yet been thoroughly examined during ageing.

    “In muscle, clonal expansion of MuSCs has been reported during tissue regeneration in response to acute injury55, but has not yet been thoroughly examined during ageing.”

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Authors
Tierney, M. T., Stec, M. J., Rulands, S., Simons, B. D., & Sacco, A.
Affiliations
  • Sanford Burnham Prebys Medical Discovery Institute (US)
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
Corresponding author
Sacco, Alessandra
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2018-01
Volume
22
Issue
1
Pages
119-127.e3
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2771380961
Cited by
92
References
45
Citations by year
2026: 11 · 2025: 7 · 2024: 5 · 2023: 11 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 15 · 2018: 6
FWCI
3.80
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • Apollo
Funders
National Institutes of Health (R01 AR064873)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
skeletal muscle stem cells, clonal complexity, tissue repair, muscle regeneration, clonal dynamics, neutral drift, proliferative capacity, tissue microenvironment, lineage tracing
MeSH terms
Aging, Animals, Cell Adhesion, Clone Cells, Homeostasis, Mice, Inbred C57BL, Models, Biological, Regeneration, Stem Cells, Stochastic Processes, Wound Healing, Muscle, Skeletal, Cell Lineage

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