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Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle

Nature Cell Biology volume 12, pages 143–152 (2010)Cite this article

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Abstract

Ectopic fat deposition in skeletal muscle is closely associated with several disorders, however, the origin of these adipocytes is not clear, nor is the mechanism of their formation. Satellite cells function as adult muscle stem cells but are proposed to possess multipotency. Here, we prospectively identify PDGFRα+ mesenchymal progenitors as being distinct from satellite cells and located in the muscle interstitium. We show that, of the muscle-derived cell populations, only PDGFRα+ cells show efficient adipogenic differentiation both in vitro and in vivo. Reciprocal transplantations between regenerating and degenerating muscles, and co-culture experiments revealed that adipogenesis of PDGFRα+ cells is strongly inhibited by the presence of satellite cell-derived myofibres. These results suggest that PDGFRα+ mesenchymal progenitors are the major contributor to ectopic fat cell formation in skeletal muscle, and emphasize that interaction between muscle cells and PDGFRα+ mesenchymal progenitors, not the fate decision of satellite cells, has a considerable impact on muscle homeostasis.

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Figure 1: In vitro adipogenic potential was found only in the PDGFRα+ population of muscle-derived cells.
Figure 2: In vitro adipogenesis of muscle-derived cells.
Figure 3: Localization of PDGFRα+ cells in adult skeletal muscle.
Figure 4: Behaviour of PDGFRα+ cells in fatty degenerating muscle.
Figure 5: Only PDGFRα+ cells differentiate into adipocytes after transplantation into glycerol-injured muscle.
Figure 6: The behaviour of PDGFRα+ cells during CTX-induced muscle regeneration and adipogenic potentials of PDGFRα+ cells isolated from regenerating or degenerating muscle.
Figure 7: The fate of PDGFRα+ cells is largely dependent on the muscle environment.
Figure 8: Satellite cell-derived myofibres inhibit adipogenic differentiation of PDGFRα+ cells.

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Acknowledgements

We thank S. Miura, M. Nakatani and T. Sato for technical assistance, F. Rossi for providing DyLight 649-conjugated rat anti-integrin α7, A. Miyajima for providing a rat anti-Dlk1 antibody and N. Hashimoto for providing a rabbit anti-myogenin antibody. This work was supported by JSPS KAKENHI (18890216; to A.U.), MEXT KAKENHI (21790884; to A.U.), a research grant (H20-018) on psychiatric and neurological diseases and mental health and a research grant (20B-13) for nervous and mental disorders from the Ministry of Health, Labour and Welfare.

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Authors and Affiliations

  1. Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, 470-1192, Aichi, Japan

    Akiyoshi Uezumi & Kunihiro Tsuchida

  2. Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, 565-0871, Osaka, Japan

    So-ichiro Fukada

  3. Laboratory of Molecular Biology & Histochemistry, Fujita Health University Joint Research Laboratory, 470-1192, Aichi, Japan

    Naoki Yamamoto

  4. Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-higashi, Kodaira, 187-8502, Tokyo, Japan

    Shin'ichi Takeda

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  1. Akiyoshi Uezumi
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Contributions

A.U. was responsible for designing and performing the experiments, analysing the data and writing the manuscript; S.F. performed BM-transplantation and provided reagents; A.U. performed FACS experiment with help from N.Y.; S.T. provided reagents and materials and A.U. and K.T. coordinated the whole project.

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Correspondence to Akiyoshi Uezumi.

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The authors declare no competing financial interests.

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Uezumi, A., Fukada, Si., Yamamoto, N. et al. Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat Cell Biol 12, 143–152 (2010). https://doi.org/10.1038/ncb2014

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