Satellite cells (SC) are muscle-specific stem cells involved in muscle growth and repair in adults. The niche of SC consists of basement membrane (basal lamina), muscle fibre and supporting cells. A major component of basement membranes (BM) is laminin, a heterotrimer protein composed of α, β and γ chains. During the transition from embryonic to foetal and to adult, the muscle basement membrane is extensively remodelled. Indeed, the embryonic basement membrane that is associated with the myotome contains Laminin-111 and -511. During foetal stages, Laminin-111 and -511 are progressively replaced by Laminin-211, which is the main Laminin constituent of the adult basement membrane surrounding muscle fibres. As similarities exist between the myogenic programme carried out by satellite cells and that executed by embryonic muscle progenitor cells, I hypothesized that the composition of the basal lamina in adult muscles may be dynamic at the site of satellite cells to support their activation and progression through myogenesis. In this study, immunofluorescence and quantitative PCR data on ex-vivo culture system of mouse extensor digitorum longus (EDL) muscle fibres revealed the expression of Laminin a1 at the site of activated satellite cells, in contrast to previous reports showing that the adult skeletal muscle basal lamina has a uniform Laminin composition (Laminin- 211). Laminin a1 association with activated satellite cells was also observed in vivo in two distinct models of muscle regeneration, the Dystrophin-deficient mdx mouse and in cardiotoxin-injured tibialis anterior (TA) muscles. Laminin a1, secreted by satellite cells, is also expressed at the surface of macrophages in vivo. Finally, I provide evidence that Integrin α6β1, the preferred receptor for Laminin a1, is expressed at the surface of activated satellite cells ex-vivo. Altogether these results reveal that a remodelling of the basal lamina occurs during skeletal muscle regeneration with the concomitant secretion and deposition of Laminin α1 in the basal lamina overlying activated satellite cells. Laminin a1 may signal through its specific receptor Integrin α6β1 to promote satellite cell progression through myogenesis. Finally, the presence of Laminin a1 may also act as a mediator between activated satellite cells and macrophages, promoting the recruitment of macrophages to the vicinity of satellite cells to support muscle regeneration. Thus, this study provides an insight into a mechanism allowing for the remodelling of the satellite cell niche during muscle regeneration.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:619083 |
| Date | January 2014 |
| Creators | Rayagiri, Shanti sree Sandeepani |
| Contributors | Borycki, Anne-Gaelle |
| Publisher | University of Sheffield |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.whiterose.ac.uk/6713/ |
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