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, Anne Gaëlle Borycki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

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.

Original languageEnglish
Article number1075
JournalNature Communications
Volume9
Issue number1
Early online date14 Mar 2018
DOIs
Publication statusPublished - Dec 2018

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