Collagen VI regulates satellite cell self-renewal and muscle regeneration

Anna Urciuolo, Marco Quarta, Valeria Morbidoni, Francesca Gattazzo, Sibilla Molon, Paolo Grumati, Francesca Montemurro, Francesco Saverio Tedesco, Bert Blaauw, Giulio Cossu, Giovanni Vozzi, Thomas A. Rando () and Paolo Bonaldo ()
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Anna Urciuolo: University of Padova
Marco Quarta: Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine
Valeria Morbidoni: University of Padova
Francesca Gattazzo: University of Padova
Sibilla Molon: University of Padova
Paolo Grumati: University of Padova
Francesca Montemurro: University of Pisa
Francesco Saverio Tedesco: University College London
Bert Blaauw: University of Padova
Giulio Cossu: University College London
Giovanni Vozzi: University of Pisa
Thomas A. Rando: Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine
Paolo Bonaldo: University of Padova

Nature Communications, 2013, vol. 4, issue 1, 1-13

Abstract: Abstract Adult muscle stem cells, or satellite cells have essential roles in homeostasis and regeneration of skeletal muscles. Satellite cells are located within a niche that includes myofibers and extracellular matrix. The function of specific extracellular matrix molecules in regulating SCs is poorly understood. Here, we show that the extracellular matrix protein collagen VI is a key component of the satellite cell niche. Lack of collagen VI in Col6a1–/– mice causes impaired muscle regeneration and reduced satellite cell self-renewal capability after injury. Collagen VI null muscles display significant decrease of stiffness, which is able to compromise the in vitro and in vivo activity of wild-type satellite cells. When collagen VI is reinstated in vivo by grafting wild-type fibroblasts, the biomechanical properties of Col6a1–/– muscles are ameliorated and satellite cell defects rescued. Our findings establish a critical role for an extracellular matrix molecule in satellite cell self-renewal and open new venues for therapies of collagen VI-related muscle diseases.

Date: 2013
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DOI: 10.1038/ncomms2964

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