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Self-renewal and expansion of single transplanted muscle stem cells
Open accessAbstract
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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“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.”
From The central role of muscle stem cells in regenerative failure with aging (2015) · cites this paper as [10]
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“In mice, transplantation of satellite cells into damaged muscle leads to self-renewal and muscle regeneration466,467.”
From Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies (2018) · cites this paper as [467]
In the citing paper
“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.”
From The central role of muscle stem cells in regenerative failure with aging (2015) · cites this paper as [10]
In the citing paper
“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.”
From The central role of muscle stem cells in regenerative failure with aging (2015) · cites this paper as [10]
In the citing paper
“MuSC were then isolated by FACS to >90% purity for all genotypes (Fig. S4), as previously described (Sacco et al., 2008)”
From Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice (2010) · cites this paper as Sacco et al., 2008
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Metadata
- 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
- PMC
- PMC2919355
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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