Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/ncomms8713
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Funding
- National Basic Research Program of China [2011CBA01104, 2011CB965002, 2014CB964703]
- National Natural Science Foundation of China [31030041, 31271470, 91019010]
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Skeletal muscle stem cells, called satellite cells, are a quiescent heterogeneous population. Their heterogeneity is influenced by Pax7, a well-defined transcriptional regulator of satellite cell functions that defines two subpopulations: Pax7Hi and Pax7(Lo). However, the mechanisms by which these subpopulations are established and maintained during myogenesis are not completely understood. Here we show that miR-431, which is predominantly expressed in the skeletal muscle, mediates satellite cell heterogeneity by fine-tuning Pax7 levels during muscle development and regeneration. In miR-431 transgenic mice, the Pax7(Lo) subpopulation is enriched, enhances myogenic differentiation and accelerates muscle regeneration. Notably, miR-431 attenuates the muscular dystrophic phenotype in mdx mice and may be a potential therapeutic target in muscular diseases. miR-431 transgenic mice are a unique genetic model for investigating the cellular features and biological functions of Pax7(Lo) satellite cells during muscle development and regeneration.
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