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Self-renewal and expansion of single transplanted muscle stem cells


Adult muscle satellite cells have a principal role in postnatal skeletal muscle growth and regeneration1. Satellite cells reside as quiescent cells underneath the basal lamina that surrounds muscle fibres2 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 isolated3,4,5 or satellite cells derived from the transplantation of one intact myofibre6 contribute robustly to muscle repair. However, because satellite cells are known to be heterogeneous4,6,7, 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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Figure 1: Characterization of the integrin-α 7 + CD34 + fraction as muscle stem cells.
Figure 2: MuSC engraftment monitored by in vivo non-invasive bioluminescence imaging.
Figure 3: MuSC proliferation in response to muscle tissue damage.
Figure 4: Transplantation of a single MuSC demonstrates self-renewal capacity.


  1. Charge, S. B. & Rudnicki, M. A. Cellular and molecular regulation of muscle regeneration. Physiol. Rev. 84, 209–238 (2004)

    CAS  Article  Google Scholar 

  2. Mauro, A. Satellite cells of skeletal muscle fibers. J. Biophys. Biochem. Cytol. 9, 493–495 (1961)

    CAS  Article  Google Scholar 

  3. Montarras, D. et al. Direct isolation of satellite cells for skeletal muscle regeneration. Science 309, 2064–2067 (2005)

    ADS  CAS  Article  Google Scholar 

  4. Kuang, S. et al. Asymmetric self-renewal and commitment of satellite stem cells in muscle. Cell 129, 999–1010 (2007)

    CAS  Article  Google Scholar 

  5. Cerletti, M. et al. Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles. Cell 134, 37–47 (2008)

    CAS  Article  Google Scholar 

  6. Collins, C. A. et al. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122, 289–301 (2005)

    CAS  Article  Google Scholar 

  7. Sherwood, R. I. et al. Isolation of adult mouse myogenic precursors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell 119, 543–554 (2004)

    CAS  Article  Google Scholar 

  8. Tajbakhsh, S. et al. Gene targeting the myf-5 locus with nlacZ reveals expression of this myogenic factor in mature skeletal muscle fibers as well as early embryonic muscle. Dev. Dyn. 206, 291–300 (1996)

    CAS  Article  Google Scholar 

  9. Seale, P. et al. Pax7 is required for the specification of myogenic satellite cells. Cell 102, 777–786 (2000)

    CAS  Article  Google Scholar 

  10. Zammit, P. S. et al. Kinetics of myoblast proliferation show that resident satellite cells are competent to fully regenerate skeletal muscle fibers. Exp. Cell Res. 281, 39–49 (2002)

    CAS  Article  Google Scholar 

  11. Zammit, P. S. et al. Muscle satellite cells adopt divergent fates: a mechanism for self-renewal? J. Cell Biol. 166, 347–357 (2004)

    CAS  Article  Google Scholar 

  12. Conboy, I. M. & Rando, T. A. The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev. Cell 3, 397–409 (2002)

    CAS  Article  Google Scholar 

  13. Boutet, S. C. et al. Regulation of Pax3 by proteasomal degradation of monoubiquitinated protein in skeletal muscle progenitors. Cell 130, 349–362 (2007)

    CAS  Article  Google Scholar 

  14. Wakeford, S., Watt, D. J. & Partridge, T. A. X-irradiation improves mdx mouse muscle as a model of myofiber loss in DMD. Muscle Nerve 14, 42–50 (1991)

    CAS  Article  Google Scholar 

  15. Heslop, L., Morgan, J. E. & Partridge, T. A. Evidence for a myogenic stem cell that is exhausted in dystrophic muscle. J. Cell Sci. 113, 2299–2308 (2000)

    CAS  PubMed  Google Scholar 

  16. Harris, J. B. & Johnson, M. A. Further observations on the pathological responses of rat skeletal muscle to toxins isolated from the venom of the Australian tiger snake, Notechis scutatus scutatus . Clin. Exp. Pharmacol. Physiol. 5, 587–600 (1978)

    CAS  Article  Google Scholar 

  17. Sacco, A. et al. IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors. J. Cell Biol. 171, 483–492 (2005)

    CAS  Article  Google Scholar 

  18. Wehrman, T. S. et al. Luminescent imaging of β-galactosidase activity in living subjects using sequential reporter-enzyme luminescence. Nature Methods 3, 295–301 (2006)

    CAS  Article  Google Scholar 

  19. Blau, H. M. & Hughes, S. M. Retroviral lineage markers for assessing myoblast fate in vivo . Adv. Exp. Med. Biol. 280, 201–203 (1990)

    CAS  Article  Google Scholar 

  20. Rando, T. A. & Blau, H. M. Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy. J. Cell Biol. 125, 1275–1287 (1994)

    CAS  Article  Google Scholar 

  21. Rando, T. A., Pavlath, G. K. & Blau, H. M. The fate of myoblasts following transplantation into mature muscle. Exp. Cell Res. 220, 383–389 (1995)

    CAS  Article  Google Scholar 

  22. Gussoni, E., Blau, H. M. & Kunkel, L. M. The fate of individual myoblasts after transplantation into muscles of DMD patients. Nature Med. 3, 970–977 (1997)

    CAS  Article  Google Scholar 

  23. Cao, Y. A. et al. Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc. Natl Acad. Sci. USA 101, 221–226 (2004)

    ADS  CAS  Article  Google Scholar 

  24. Barberi, T. et al. Derivation of engraftable skeletal myoblasts from human embryonic stem cells. Nature Med. 13, 642–648 (2007)

    CAS  Article  Google Scholar 

  25. Osawa, M. et al. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273, 242–245 (1996)

    ADS  CAS  Article  Google Scholar 

  26. Silberstein, L. et al. Developmental progression of myosin gene expression in cultured muscle cells. Cell 46, 1075–1081 (1986)

    CAS  Article  Google Scholar 

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We thank O. Alkan for developing the single cell RT–PCR protocol, K. Koleckar, M. Pajcini and T. Doyle for technical support, T. Brazelton, F. Rossi and S. Corbel for comments on the manuscript, J. Ramunas for statistical analysis, and M. Lutolf and P. Gilbert for fabricating the hydrogel microwells. We also thank F. Rossi for providing the integrin-α7–PE-conjugated antibody, and C. Contag for providing the FLuc mice. This work was supported by NIH grants AG009521, AG024987 and by the Baxter Foundation.

Author Contributions A.S., H.M.B. and R.D. designed the research, and A.S. and R.D. performed the experiments with support from P.K. S.V. performed single-cell RT–PCR. A.S. analysed the data. A.S., R.D. and H.M.B. discussed the results and wrote the paper.

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Correspondence to Helen M. Blau.

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Sacco, A., Doyonnas, R., Kraft, P. et al. Self-renewal and expansion of single transplanted muscle stem cells. Nature 456, 502–506 (2008).

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