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Muscle stem cells differentiate into haematopoietic lineages but retain myogenic potential

Abstract

Muscle-derived stem cells (MDSCs) can differentiate into multiple lineages, including haematopoietic lineages1,2,3,4,5,6,7,8,9,10,11,12. However, it is unknown whether MDSCs preserve their myogenic potential after differentiation into other lineages. To address this issue, we isolated from dystrophic muscle a population of MDSCs that express stem-cell markers and can differentiate into various lineages1,13. After systemic delivery of three MDSC clones into lethally irradiated mice, we found that differentiation of the donor cells into various lineages of the haematopoietic system resulted in repopulation of the recipients' bone marrow. Donor-derived bone-marrow cells, isolated from these recipients by fluorescence-activated cell sorting (FACS), also repopulated the bone marrow of secondary, lethally irradiated, recipients and differentiated into myogenic cells both in vitro and in vivo in normal mdx mice. These findings demonstrate that MDSC clones retain their myogenic potential after haematopoietic differentiation.

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Figure 1: Systemic transplantation of MDSCs.
Figure 2: Transplantation of MDSCs into lethally irradiated SJL/J mice.
Figure 3: In vitro and in vivo examination of recovered donor cells.

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References

  1. Lee, J.Y. et al. Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J. Cell Biol. 150, 1085–1100 (2000).

    Article  CAS  Google Scholar 

  2. Gussoni, E. et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401, 390–394 (1999).

    CAS  Google Scholar 

  3. Seale, P., Asakura, A. & Rudnicki, M.A. The potential of muscle stem cells. Dev. Cell 1, 333–342 (2001).

    Article  CAS  Google Scholar 

  4. Goodell, M.A. et al. Stem cell plasticity in muscle and bone marrow. Ann. NY Acad. Sci. 938, 208–220 (2001).

    Article  CAS  Google Scholar 

  5. Jackson, K.A., Mi, T. & Goodell, M.A. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc. Natl Acad. Sci. USA 96, 14482–14486 (1999).

    Article  CAS  Google Scholar 

  6. McKinney-Freeman, S.L. et al. Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc. Natl Acad. Sci. USA 99, 1341–1346 (2002).

    Article  CAS  Google Scholar 

  7. Blau, H.M., Brazelton, T.R. & Weimann, J.M. The evolving concept of a stem cell: entity or function? Cell 105, 829–841 (2001).

    Article  CAS  Google Scholar 

  8. Torrente, Y. et al. Intraarterial injection of muscle-derived CD34(+)Sca-1(+) stem cells restores dystrophin in mdx mice. J. Cell Biol. 152, 335–348 (2001).

    Article  CAS  Google Scholar 

  9. Kawada, H. & Ogawa, M. Bone marrow origin of hematopoietic progenitors and stem cells in murine muscle. Blood 98, 2008–2013 (2001).

    Article  CAS  Google Scholar 

  10. Jackson, K.A., Majka, S.M., Wulf, G.G. & Goodell, M.A. Stem cells: a minireview. J. Cell Biochem. Suppl. 38, 1–6 (2002).

    Article  Google Scholar 

  11. Goldring, K., Partridge, T. & Watt, D. Muscle stem cells. J. Pathol. 197, 457–467 (2002).

    Article  Google Scholar 

  12. Jiang, Y. et al. Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp. Hematol. 30, 896–904 (2002).

    Article  CAS  Google Scholar 

  13. Qu-Petersen, Z. et al. Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. J. Cell Biol. 157, 851–864 (2002).

    Article  CAS  Google Scholar 

  14. Qu, Z. et al. Development of approaches to improve cell survival in myoblast transfer therapy. J. Cell Biol. 142, 1257–1267 (1998).

    Article  CAS  Google Scholar 

  15. 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).

    Article  CAS  Google Scholar 

  16. Richler, C. & Yaffe, D. The in vitro cultivation and differentiation capacities of myogenic cell lines. Dev. Biol. 23, 1–22 (1970).

    Article  CAS  Google Scholar 

  17. Hoffman, E.P., Brown, R.H., Jr & Kunkel, L.M. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51, 919–928 (1987).

    Article  CAS  Google Scholar 

  18. Lewis, J.L. et al. The influence of INK4 proteins on growth and self-renewal kinetics of hematopoietic progenitor cells. Blood 97, 2604–2610 (2001).

    Article  CAS  Google Scholar 

  19. Terada, N. et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416, 542–545 (2002).

    Article  CAS  Google Scholar 

  20. Ying, Q.L., Nichols, J., Evans, E.P. & Smith, A.G. Changing potency by spontaneous fusion. Nature 416, 545–548 (2002).

    Article  CAS  Google Scholar 

  21. Goepfert, T.M. et al. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells. FASEB J. 14, 2221–2229 (2000).

    Article  CAS  Google Scholar 

  22. Kubota, C. et al. Six cloned calves produced from adult fibroblast cells after long-term culture. Proc. Natl Acad. Sci. USA 97, 990–995 (2000).

    Article  CAS  Google Scholar 

  23. Wagers, A.J., Sherwood, R.I., Christensen, J.L. & Weissman, I.L. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297, 2256–2259 (2002).

    Article  CAS  Google Scholar 

  24. Bittner, R.E. et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat. Embryol. (Berl.) 199, 391–396 (1999).

    Article  CAS  Google Scholar 

  25. Ferrari, G. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279, 1528–1530 (1998).

    Article  CAS  Google Scholar 

  26. LaBarge, M.A. & Blau, H.M. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 111, 589–601 (2002).

    Article  CAS  Google Scholar 

  27. Geiger, H. et al. Analysis of the hematopoietic potential of muscle-derived cells in mice. Blood 100, 721–723 (2002).

    Article  CAS  Google Scholar 

  28. Yuasa, K. et al. Effective restoration of dystrophin-associated proteins in vivo by adenovirus-mediated transfer of truncated dystrophin cDNAs. FEBS Lett. 425, 329–336 (1998).

    Article  CAS  Google Scholar 

  29. Barch, M. The ACT cytogenetics laboratory manual (Raven Press Ltd, New York, 1991).

    Google Scholar 

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Acknowledgements

This work was supported by the National Institutes of Health (PO1 AR 45925, RO1 AR 49684-01), the Muscular Dystrophy Association (USA), the Jean W. Donaldson Chair at Children's Hospital of Pittsburgh and the Henry J. Mankin Endowed Chair of the University of Pittsburgh. The authors wish to thank M. Pellerin, R. Pruchnic, R. Lakomy, W.A. Rudert, Y. Fan and M. Trucco for technical contributions, as well as R. Sauder for his outstanding assistance with the manuscript.

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Correspondence to Johnny Huard.

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J. Huard receives a consultant fee from Cook Myosite

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Cao, B., Zheng, B., Jankowski, R. et al. Muscle stem cells differentiate into haematopoietic lineages but retain myogenic potential. Nat Cell Biol 5, 640–646 (2003). https://doi.org/10.1038/ncb1008

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