Muscle Stem Cells Exhibit Distinct Clonal Dynamics in Response to Tissue Repair and Homeostatic Aging
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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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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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [55]
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Healthy skeletal muscle aging: The role of satellite cells, somatic mutations and exercise
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Stem cells in skeletal muscle growth and regeneration in amniotes and teleosts: Emerging themes
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Single-cell analyses uncover granularity of muscle stem cells
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Muscle Stem Cell Microenvironment and Functions in Muscle Regeneration
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Epigenetic control of muscle stem cells: time for a new dimension
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Mechanism of age-related accumulation of mtDNA mutations in human blood
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Aging-associated stem/progenitor cell dysfunction in the salivary glands of mice
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Nutrition and stem cell integrity in aging
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Regulation of muscle stem cell function
von Maltzahn, J. (2021) · Vitamins and hormones · doi:10.1016/bs.vh.2021.02.012 · Cited by 8 · see citing works
Clonal selection parallels between normal and cancer tissues
Salavaty, A., Azadian, E., Naik, S. H., & Currie, P. D. (2023) · Trends in Genetics · doi:10.1016/j.tig.2023.01.007 · Cited by 8 · see citing works
Human skeletal muscle ageing atlasPreprint
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Clonal behaviour of myogenic precursor cells throughout the vertebrate lifespan
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The proliferation and differentiation of skeletal muscle stem cells are enhanced in a bioreactor
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Self-citationImpact of vitamin D and vitamin D receptor TaqI polymorphism in primary human myoblasts
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microRNA-501 controls myogenin+/CD74+ myogenic progenitor cells during muscle regeneration
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Assessing Muscle Stem Cell Clonal Complexity During Aging
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Self-citationMechanism of age-related accumulation of mitochondrial DNA mutations in human bloodPreprint
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Skeletal Muscle Aging: Lessons From Teleosts
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Regulation and function of Pax3 in muscle stem cell heterogeneity and stress response
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Muscle stem cells trade functionality for survival
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Age-Related Variation in DNA Methylation
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Self-citationEpigenetic Regulation of Muscle Stem Cells During Skeletal Muscle Regeneration and Disease
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Satellite Cells in Regeneration and DiseasePreprint
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Clonal behaviour of myogenic precursor cells throughout the vertebrate lifespanPreprint
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PAX3-SIX2 muscle stem cell heterogeneity drives muscle-specific repair dynamics diversification
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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
- PMC
- PMC5945549
- 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
- bronze
- doi.org
- Licence
- 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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