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The aged niche disrupts muscle stem cell quiescence

Author

Listed:
  • Joe V. Chakkalakal

    (Center of Regenerative Medicine, Massachusetts General Hospital)

  • Kieran M. Jones

    (King’s College London, Guy’s Campus, London SE1 9RT, UK)

  • M. Albert Basson

    (King’s College London, Guy’s Campus, London SE1 9RT, UK)

  • Andrew S. Brack

    (Center of Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, 135 Massachusetts Avenue
    Harvard Medical School, 25 Shattuck Street)

Abstract

The niche is a conserved regulator of stem cell quiescence and function. During ageing, stem cell function declines. To what extent and by what means age-related changes within the niche contribute to this phenomenon are unknown. Here we demonstrate that the aged muscle stem cell niche, the muscle fibre, expresses Fgf2 under homeostatic conditions, driving a subset of satellite cells to break quiescence and lose their self-renewing capacity. We show in mice that relatively dormant aged satellite cells robustly express sprouty 1 (Spry1), an inhibitor of fibroblast growth factor (FGF) signalling. Increasing FGF signalling in aged satellite cells under homeostatic conditions by removing Spry1 results in the loss of quiescence, satellite cell depletion and diminished regenerative capacity. Conversely, reducing niche-derived FGF activity through inhibition of Fgfr1 signalling or overexpression of Spry1 in satellite cells prevents their depletion. These experiments identify an age-dependent change in the stem cell niche that directly influences stem cell quiescence and function.

Suggested Citation

  • Joe V. Chakkalakal & Kieran M. Jones & M. Albert Basson & Andrew S. Brack, 2012. "The aged niche disrupts muscle stem cell quiescence," Nature, Nature, vol. 490(7420), pages 355-360, October.
    • Handle: RePEc:nat:nature:v:490:y:2012:i:7420:d:10.1038_nature11438
    DOI: 10.1038/nature11438
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    Cited by:

    1. David E. Lee & Lauren K. McKay & Akshay Bareja & Yongwu Li & Alastair Khodabukus & Nenad Bursac & Gregory A. Taylor & Gurpreet S. Baht & James P. White, 2022. "Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Brendan Evano & Diljeet Gill & Irene Hernando-Herraez & Glenda Comai & Thomas M Stubbs & Pierre-Henri Commere & Wolf Reik & Shahragim Tajbakhsh, 2020. "Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation," PLOS Genetics, Public Library of Science, vol. 16(10), pages 1-21, October.
    3. Jeffrey C. Gerrard & Jamison P. Hay & Ryan N. Adams & James C. Williams & Joshua R. Huot & Kaitlin M. Weathers & Joseph S. Marino & Susan T. Arthur, 2021. "Current Thoughts of Notch’s Role in Myoblast Regulation and Muscle-Associated Disease," IJERPH, MDPI, vol. 18(23), pages 1-20, November.
    4. Felicia Lazure & Rick Farouni & Korin Sahinyan & Darren M. Blackburn & Aldo Hernández-Corchado & Gabrielle Perron & Tianyuan Lu & Adrien Osakwe & Jiannis Ragoussis & Colin Crist & Theodore J. Perkins , 2023. "Transcriptional reprogramming of skeletal muscle stem cells by the niche environment," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Adelaida R. Palla & Keren I. Hilgendorf & Ann V. Yang & Jaclyn P. Kerr & Aaron C. Hinken & Janos Demeter & Peggy Kraft & Nancie A. Mooney & Nora Yucel & David M. Burns & Yu Xin Wang & Peter K. Jackson, 2022. "Primary cilia on muscle stem cells are critical to maintain regenerative capacity and are lost during aging," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Xiaoyan Wei & Angelos Rigopoulos & Matthias Lienhard & Sophie Pöhle-Kronawitter & Georgios Kotsaris & Julia Franke & Nikolaus Berndt & Joy Orezimena Mejedo & Hao Wu & Stefan Börno & Bernd Timmermann &, 2024. "Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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