Sphingosine-1-phosphate receptor 3 influences cell cycle progression in muscle satellite cells |
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Authors: | Mathieu Fortier Nicolas FigeacRobert B White Paul Knopp Peter S Zammit |
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Institution: | King′s College London, Randall Division of Cell and Molecular Biophysics, New Hunt′s House, Guy′s Campus, London, SE1 1UL, UK |
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Abstract: | Skeletal muscle retains a resident stem cell population called satellite cells, which are mitotically quiescent in mature muscle, but can be activated to produce myoblast progeny for muscle homeostasis, hypertrophy and repair. We have previously shown that satellite cell activation is partially controlled by the bioactive phospholipid, sphingosine-1-phosphate, and that S1P biosynthesis is required for muscle regeneration. Here we investigate the role of sphingosine-1-phosphate receptor 3 (S1PR3) in regulating murine satellite cell function. S1PR3 levels were high in quiescent myogenic cells before falling during entry into cell cycle. Retrovirally-mediated constitutive expression of S1PR3 led to suppressed cell cycle progression in satellite cells, but did not overtly affect the myogenic program. Conversely, satellite cells isolated from S1PR3-null mice exhibited enhanced proliferation ex-vivo. In vivo, acute cardiotoxin-induced muscle regeneration was enhanced in S1PR3-null mice, with bigger muscle fibres compared to control mice. Importantly, genetically deleting S1PR3 in the mdx mouse model of Duchenne muscular dystrophy produced a less severe muscle dystrophic phenotype, than when signalling though S1PR3 was operational. In conclusion, signalling though S1PR3 suppresses cell cycle progression to regulate function in muscle satellite cells. |
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Keywords: | Stem cell Satellite cell Skeletal muscle Sphingosine-1-phosphate S1PR3 Muscular dystrophy mdx Regeneration Cell cycle Proliferation Quiescence |
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