Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal

Shantisree Sandeepani Rayagiri, Daniele Ranaldi, Alexander Raven, Nur Izzah Farhana Mohamad Azhar, Olivier Lefebvre, Peter S Zammit and Anne-Gaëlle Borycki ()
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Shantisree Sandeepani Rayagiri: University of Sheffield, Firth Court
Daniele Ranaldi: University of Sheffield, Firth Court
Alexander Raven: University of Sheffield, Firth Court
Nur Izzah Farhana Mohamad Azhar: University of Sheffield, Firth Court
Olivier Lefebvre: Inserm U1109 MN3T
Peter S Zammit: New Hunt’s House
Anne-Gaëlle Borycki: University of Sheffield, Firth Court

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract A central question in stem cell biology is the relationship between stem cells and their niche. Although previous reports have uncovered how signaling molecules released by niche cells support stem cell function, the role of the extra-cellular matrix (ECM) within the niche is unclear. Here, we show that upon activation, skeletal muscle stem cells (satellite cells) induce local remodeling of the ECM and the deposition of laminin-α1 and laminin-α5 into the basal lamina of the satellite cell niche. Genetic ablation of laminin-α1, disruption of integrin-α6 signaling or blocking matrix metalloproteinase activity impairs satellite cell expansion and self-renewal. Collectively, our findings establish that remodeling of the ECM is an integral process of stem cell activity to support propagation and self-renewal, and may explain the effect laminin-α1-containing supports have on embryonic and adult stem cells, as well as the regenerative activity of exogenous laminin-111 therapy.

Date: 2018
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DOI: 10.1038/s41467-018-03425-3

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