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Tissue-Specific Stem Cells
Version of Record online: 20 SEP 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 10, pages 2330–2341, October 2012
How to Cite
Ross, J., Benn, A., Jonuschies, J., Boldrin, L., Muntoni, F., Hewitt, J. E., Brown, S. C. and Morgan, J. E. (2012), Defects in Glycosylation Impair Satellite Stem Cell Function and Niche Composition in the Muscles of the Dystrophic Largemyd Mouse. STEM CELLS, 30: 2330–2341. doi: 10.1002/stem.1197
Author contributions: J.R.: collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; A.B., J.J., and L.B.: collection and/or assembly of data and final approval of manuscript; F.M.: conception and design, financial support, and final approval of manuscript; J.E.H.: conception and design, manuscript writing, and final approval of manuscript; S.C.B. and J.E.M.: conception and design, financial support, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS August 9, 2012.
- Issue online: 20 SEP 2012
- Version of Record online: 20 SEP 2012
- Accepted manuscript online: 9 AUG 2012 07:56AM EST
- Manuscript Accepted: 22 JUN 2012
- Manuscript Revised: 8 JUN 2012
- Manuscript Received: 9 FEB 2012
- Skeletal muscle satellite cells;
- Adult stem cells;
- Congenital muscular dystrophy;
- Extracellular matrix;
- Muscle regeneration
The dystrophin-associated glycoprotein complex (DGC) is found at the muscle fiber sarcolemma and forms an essential structural link between the basal lamina and internal cytoskeleton. In a set of muscular dystrophies known as the dystroglycanopathies, hypoglycosylation of the DGC component α-dystroglycan results in reduced binding to basal lamina components, a loss in structural stability, and repeated cycles of muscle fiber degeneration and regeneration. The satellite cells are the key stem cells responsible for muscle repair and reside between the basal lamina and sarcolemma. In this study, we aimed to determine whether pathological changes associated with the dystroglycanopathies affect satellite cell function. In the Largemyd mouse dystroglycanopathy model, satellite cells are present in significantly greater numbers but display reduced proliferation on their native muscle fibers in vitro, compared with wild type. However, when removed from their fiber, proliferation in culture is restored to that of wild type. Immunohistochemical analysis of Largemyd muscle reveals alterations to the basal lamina and interstitium, including marked disorganization of laminin, upregulation of fibronectin and collagens. Proliferation and differentiation of wild-type satellite cells is impaired when cultured on substrates such as collagen and fibronectin, compared with laminins. When engrafted into irradiated tibialis anterior muscles of mdx-nude mice, wild-type satellite cells expanded on laminin contribute significantly more to muscle regeneration than those expanded on fibronectin. These results suggest that defects in α-dystroglycan glycosylation are associated with an alteration in the satellite cell niche, and that regenerative potential in the dystroglycanopathies may be perturbed. STEM Cells2012;30:2330–2341