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

doi:10.1038/s41467-018-03425-3

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 journal › Article › peer-review

127 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 language	English
Article number	1075
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	14 Mar 2018
DOIs	https://doi.org/10.1038/s41467-018-03425-3
Publication status	Published - Dec 2018

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title = "Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal",

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.",

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AU - Rayagiri, Shantisree Sandeepani

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AU - Mohamad Azhar, Nur Izzah Farhana

AU - Lefebvre, Olivier

AU - Zammit, Peter S.

AU - Borycki, Anne Gaëlle

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AB - 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.

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

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