Cited by 901Muscle Physiology and DisordersMesenchymal stem cell researchCongenital heart defects research

Self-renewal and expansion of single transplanted muscle stem cells

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Sacco, Alessandra, Doyonnas, Regis, Kraft, Peggy, Vitorovic, Stefan, Blau, Helen M.·2008·Nature

Abstract

Adult muscle satellite cells have a principal role in postnatal skeletal muscle growth and regeneration. Satellite cells reside as quiescent cells underneath the basal lamina that surrounds muscle fibres and respond to damage by giving rise to transient amplifying cells (progenitors) and myoblasts that fuse with myofibres. Recent experiments showed that, in contrast to cultured myoblasts, satellite cells freshly isolated or satellite cells derived from the transplantation of one intact myofibre contribute robustly to muscle repair. However, because satellite cells are known to be heterogeneous, clonal analysis is required to demonstrate stem cell function. Here we show that when a single luciferase-expressing muscle stem cell is transplanted into the muscle of mice it is capable of extensive proliferation, contributes to muscle fibres, and Pax7(+)luciferase(+) mononucleated cells can be readily re-isolated, providing evidence of muscle stem cell self-renewal. In addition, we show using in vivo bioluminescence imaging that the dynamics of muscle stem cell behaviour during muscle repair can be followed in a manner not possible using traditional retrospective histological analyses. By imaging luciferase activity, real-time quantitative and kinetic analyses show that donor-derived muscle stem cells proliferate and engraft rapidly after injection until homeostasis is reached. On injury, donor-derived mononucleated cells generate massive waves of cell proliferation. Together, these results show that the progeny of a single luciferase-expressing muscle stem cell can both self-renew and differentiate after transplantation in mice, providing new evidence at the clonal level that self-renewal is an autonomous property of a single adult muscle stem cell.

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  • In mice, transplantation of satellite cells into damaged muscle leads to self-renewal and muscle regeneration.

    “In mice, transplantation of satellite cells into damaged muscle leads to self-renewal and muscle regeneration466,467.”
  • Dedicated muscle stem cells, also called satellite cells, support repair of skeletal muscle.

    “Skeletal muscle repair is facilitated by a population of dedicated muscle stem cells (MuSCs), also known as satellite cells, that reside in anatomically defined niches within muscle tissues.”
  • Multiple rounds of self-renewing divisions by MuSCs are required for their regenerative function, as shown by transplantation, genetic ablation, and lineage tracing.

    “Subsequently, MuSCs undergo multiple rounds of self-renewing divisions that are essential to their function in regeneration, as demonstrated by transplantation, genetic ablation, and lineage tracing experiments5–12.”
  • Single MuSCs can produce thousands of progeny, differentiate into myofibers, and self-renew after re-injury.

    “By using BLI, single MuSCs isolated from transgenic mice that ubiquitously express a luciferase transgene were shown to give rise to thousands of progeny, differentiate into myofibers, and self-renew upon re-injury10.”
  • Muscle stem cells were isolated by FACS to greater than 90% purity for all genotypes.

    “MuSC were then isolated by FACS to >90% purity for all genotypes (Fig. S4), as previously described (Sacco et al., 2008)”

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Authors
Sacco, A., Doyonnas, R., Kraft, P., Vitorovic, S., & Blau, H. M.
Affiliations
Stanford Medicine (US)
Corresponding author
Blau, Helen M.
Venue
Nature
Published
2008-09-17
Volume
456
Issue
7221
Pages
502-506
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2031495223
Cited by
901
References
26
Citations by year
2026: 20 · 2025: 36 · 2024: 37 · 2023: 47 · 2022: 46 · 2021: 54 · 2020: 59 · 2019: 58 · 2018: 52 · 2017: 51 · 2016: 46 · 2015: 66 · 2014: 50 · 2013: 60 · 2012: 67
FWCI
20.59
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (AG009521, AG 024987, R37AG009521, R01AG009521, R01AG020961, R01AG024987)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
satellite cells, muscle stem cells, self-renewal, clonal analysis, single-cell transplantation, Pax7, muscle regeneration, muscle damage, bioluminescence imaging, cell proliferation, skeletal muscle
MeSH terms
Animals, Cells, Cultured, Homeostasis, Luminescent Measurements, Muscles, Regeneration, Stem Cells, Antigens, CD, Muscle Fibers, Skeletal, Antigens, CD34, Satellite Cells, Skeletal Muscle, Stem Cell Transplantation, Integrin alpha Chains, Cell Proliferation, Mice

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