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Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates

Nature Medicine volume 9, pages 1520–1527 (2003)Cite this article

A Corrigendum to this article was published on 01 January 2004

Abstract

Recent studies have shown that cells from the bone marrow can give rise to differentiated skeletal muscle fibers. However, the mechanisms and identities of the cell types involved have remained unknown, and the validity of the observation has been questioned. Here, we use transplantation of single CD45+ hematopoietic stem cells (HSCs) to demonstrate that the entire circulating myogenic activity in bone marrow is derived from HSCs and their hematopoietic progeny. We also show that ongoing muscle regeneration and inflammatory cell infiltration are required for HSC-derived contribution, which does not occur through a myogenic stem cell intermediate. Using a lineage tracing strategy, we show that myofibers are derived from mature myeloid cells in response to injury. Our results indicate that circulating myeloid cells, in response to inflammatory cues, migrate to regenerating skeletal muscle and stochastically incorporate into mature myofibers.

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Figure 1: Clonal analysis of HSC myogenic potential.
Figure 2: Muscle contribution after transplantation of single HSCs.
Figure 3: Myogenic engraftment by hematopoietic myeloid cells.
Figure 4: Failure of bone marrow cells to generate mononuclear myogenic cells.
Figure 5: Model for the mechanism of bone marrow–derived myogenesis.

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Acknowledgements

F.D.C. was a fellow of the American Liver Foundation. M.A.G. is a Scholar of the Leukemia and Lymphoma Society. K.A.J. is a fellow of the Leukemia and Lymphoma Society and of the Muscular Dystrophy Association. This work was supported by grants to M.A.G. from the Muscular Dystrophy Association and the National Institutes of Health. We thank M. Cubbage for flow cytometry assistance, F. Mavilio (HSR-TIGET, Italy) for MLacZ mice, L. Pao (Harvard) for LysM-Cre mice, and D. Burton for animal care.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, 77030, Texas, USA

    Fernando D Camargo, Rahshaana Green, Kathyjo A Jackson & Margaret A Goodell

  2. Cell and Molecular Biology Program, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, 77030, Texas, USA

    Fernando D Camargo & Margaret A Goodell

  3. Molecular Cell Biology Department, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, 77030, Texas, USA

    Yassemi Capetenaki

  4. Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, 77030, Texas, USA

    Kathyjo A Jackson & Margaret A Goodell

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Correspondence to Margaret A Goodell.

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Camargo, F., Green, R., Capetenaki, Y. et al. Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat Med 9, 1520–1527 (2003). https://doi.org/10.1038/nm963

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