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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Item Type:	Article
Authors/Creators:	Rayagiri, S.S. Ranaldi, D. Raven, A. Mohamad Azhar, I.F. Lefebvre, O. Zammit, P.S. Borycki, A.G. https://orcid.org/0000-0002-7412-3682
Copyright, Publisher and Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 13 February 2018 Published (online): 14 March 2018 Published: 14 March 2018
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield)
Funding Information:	Funder Grant number ASSOCIATION FRANCAISE CONTRE LES MYOPATHIES 16350
Depositing User:	Symplectic Sheffield
Date Deposited:	16 Apr 2018 14:46
Last Modified:	01 Nov 2018 12:33
Published Version:	https://doi.org/10.1038/s41467-018-03425-3
Status:	Published
Publisher:	Nature Publishing Group: Nature Communications
Refereed:	Yes
Identification Number:	10.1038/s41467-018-03425-3
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:129708

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

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