title: APC is required for muscle stem cell proliferation and skeletal muscle tissue repair.
abstract: The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS), UMR 8104, 75014 Paris, France Institut National de la Santé et de la Recherché Médicale (INSERM) U1016, 75014 Paris, France.
authors: Alice
authors: A
authors: Parisi
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS), UMR 8104, 75014 Paris, France Institut National de la Santé et de la Recherché Médicale (INSERM) U1016, 75014 Paris, France.
authors: Floriane
authors: F
authors: Lacour
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS), UMR 8104, 75014 Paris, France Institut National de la Santé et de la Recherché Médicale (INSERM) U1016, 75014 Paris, France.
authors: Lorenzo
authors: L
authors: Giordani
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS), UMR 8104, 75014 Paris, France Institut National de la Santé et de la Recherché Médicale (INSERM) U1016, 75014 Paris, France.
authors: Sabine
authors: S
authors: Colnot
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS), UMR 8104, 75014 Paris, France Institut National de la Santé et de la Recherché Médicale (INSERM) U1016, 75014 Paris, France.
authors: Pascal
authors: P
authors: Maire
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS), UMR 8104, 75014 Paris, France Institut National de la Santé et de la Recherché Médicale (INSERM) U1016, 75014 Paris, France fabien.le-grand@inserm.fr.
authors: Fabien
authors: F
authors: Le Grand
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000502:physiology*; D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D014945:Wound Healing / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin