title: H19 controls reactivation of the imprinted gene network during muscle regeneration.
abstract: 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(Δ3) 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(Δ3) 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.
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, University Paris Descartes, Paris 75014, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Martinet
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, University Paris Descartes, Paris 75014, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Monnier
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, University Paris Descartes, Paris 75014, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Louault
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, University Paris Descartes, Paris 75014, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Benard
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, University Paris Descartes, Paris 75014, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gabory
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR 8104, University Paris Descartes, Paris 75014, France luisa.dandolo@inserm.fr.
authors.forename: Luisa
authors.initials: L
authors.lastname: Dandolo
mesh_terms: D000818:Animals; D054715:Cardiotoxins / Q000633:toxicity; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D017353:Gene Deletion; D053263:Gene Regulatory Networks / Q000187:drug effects; D018392:Genomic Imprinting / Q000187:drug effects; D006965:Hyperplasia; D006984:Hypertrophy; D008297:Male; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D032446:Myoblasts / Q000187:drug effects / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects / Q000235:genetics*; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology
chemical_list: D054715:Cardiotoxins; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding
keywords: Epigenetics; Genomic imprinting; Mouse; Quiescence; Satellite cells