期刊
DEVELOPMENT
卷 143, 期 6, 页码 962-971出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.131771
关键词
Satellite cells; Quiescence; Genomic imprinting; Epigenetics; Mouse
资金
- Association Francaise contre les Myopathies (AFM)
- Agence Nationale de la Recherche [ANR-14-CE11-0022-02]
- Region Ile-de-France (DIM Biotherapy)
- Agence Nationale de la Recherche (ANR) [ANR-14-CE11-0022] Funding Source: Agence Nationale de la Recherche (ANR)
The H19 locus controls fetal growth by regulating expression of several genes from the imprinted gene network (IGN). H19 is fully repressed after birth, except in skeletal muscle. Using loss-of-function H19(Delta 3) mice, we investigated the function of H19 in adult muscle. Mutant muscles display hypertrophy and hyperplasia, with increased Igf2 and decreased myostatin (Mstn) expression. Many imprinted genes are expressed in muscle stem cells or satellite cells. Unexpectedly, the number of satellite cells was reduced by 50% in H19(Delta 3) muscle fibers. This reduction occurred after postnatal day 21, suggesting a link with their entry into quiescence. We investigated the biological function of these mutant satellite cells in vivo using a regeneration assay induced by multiple injections of cardiotoxin. Surprisingly, despite their reduced number, the self-renewal capacity of these cells is fully retained in the absence of H19. In addition, we observed a better regeneration potential of the mutant muscles, with enhanced expression of several IGN genes and genes from the IGF pathway.
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