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Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis

Nature Cell Biology volume 12, pages 153–163 (2010)Cite this article

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Abstract

Efficient tissue regeneration is dependent on the coordinated responses of multiple cell types. Here, we describe a new subpopulation of fibro/adipogenic progenitors (FAPs) resident in muscle tissue but arising from a distinct developmental lineage. Transplantation of purified FAPs results in the generation of ectopic white fat when delivered subcutaneously or intramuscularly in a model of fatty infiltration, but not in healthy muscle, suggesting that the environment controls their engraftment. These cells are quiescent in intact muscle but proliferate efficiently in response to damage. FAPs do not generate myofibres, but enhance the rate of differentiation of primary myogenic progenitors in co-cultivation experiments. In summary, FAPs expand upon damage to provide a transient source of pro-differentiation signals for proliferating myogenic progenitors.

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Figure 1: Prospective isolation of progenitor populations from skeletal muscle.
Figure 2: Lin−Sca-1+CD34+ cells generate both fibroblasts and adipocytes.
Figure 3: Developmental potential of sorted progenitor populations in vivo.
Figure 4: Skeletal muscle-derived FAPs and MPs have distinct developmental potentials and do not arise from a common progenitor.
Figure 5: FAPs proliferate in response to muscle damage.
Figure 6: FAPs are in close proximity to myofibres after damage.
Figure 7: FAPs enhance myogenic differentiation.

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Acknowledgements

We thank J. Qiao, C. Chang, J. M. Joe, the BRC Animal Facility, the BRC Core Staff and A. Johnson and J. Duenas of the UBC FACS Facility for their expert technical assistance. We are also grateful to A. Uezumi for advice on modelling fatty degeneration in murine skeletal muscle. This research was supported by grants from The Foundation for Cell therapy (Jesse's Journey) and The Canadian Institute for Health Research (CIHR MOP-97856; CSB-94219; MUS-94019) to F.M.V.R. who holds a Canada Research Chair in Regenerative medicine and is a fellow of the Michael Smith Foundation for Health Research. A.W.B.J. is supported by a fellowship from CIHR, A.N. from the Heart and Stroke Foundation of Canada and L.S. from NSERC (PGSD2-362406-2008).

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Author notes

  1. Lin Yi and Anuradha Natarajan: These authors contributed equally to this work.

Authors and Affiliations

  1. The Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver BC, V6T 1Z3, Canada

    Aaron W. B. Joe, Lin Yi, Anuradha Natarajan, Leslie So, Joy Wang & Fabio M. V. Rossi

  2. MD/PhD Program, Faculty of Medicine, The University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, V6T 1Z3, BC, Canada

    Aaron W. B. Joe

  3. Department of Medical Genetics, Faculty of Medicine, The University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, V6T 1Z3, BC, Canada

    Fabio M. V. Rossi

  4. The Sprott Center for Stem Cell Research, Ottawa Health Research Institute, Molecular Medicine Program, 501 Smyth Road, Ottawa, K1H 8L6, ON, Canada

    Fabien Le Grand & Michael A. Rudnicki

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Contributions

A.W.B.J. designed and performed experiments, analysed data, interpreted results and wrote the manuscript. L.Y. and A.N. designed and performed experiments and analysed data. L.S. and J.W. performed experiments. F.L. and M.A.R. provided new reagents and performed experiments. F.M.V.R. designed and performed experiments, interpreted results and wrote the manuscript.

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Correspondence to Fabio M. V. Rossi.

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Joe, A., Yi, L., Natarajan, A. et al. Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat Cell Biol 12, 153–163 (2010). https://doi.org/10.1038/ncb2015

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