title: β-Catenin Activation in Muscle Progenitor Cells Regulates Tissue Repair.
abstract: Skeletal muscle regeneration relies on a pool of resident muscle stem cells called satellite cells (MuSCs). Following injury-induced destruction of the myofibers, quiescent MuSCs are activated and generate transient amplifying progenitors (myoblasts) that will fuse to form new myofibers. Here, we focus on the canonical Wnt signaling pathway and find that either conditional β-catenin disruption or activation in adult MuSCs results in perturbation of muscle regeneration. Using both in vivo and in vitro approaches, we observed that myoblasts lacking β-catenin show delayed differentiation, whereas myoblasts with constitutively active β-catenin undergo precocious growth arrest and differentiation. Transcriptome analysis further demonstrated that Wnt/β-catenin signaling interacts with multiple pathways and, more specifically, TGF-β signaling. Indeed, exogenous TGF-β2 stimulation restores the regenerative potential of muscles with targeted β-catenin disruption in MuSCs. We conclude that a precise level of β-catenin activity is essential for regulating the amplification and differentiation of MuSC descendants during adult myogenesis.
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Anja
authors.initials: A
authors.lastname: Rudolf
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France; Sorbonne Universités, UPMC Université Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, 75013 Paris, France.
authors.forename: Elija
authors.initials: E
authors.lastname: Schirwis
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France; Sorbonne Universités, UPMC Université Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, 75013 Paris, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Giordani
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Parisi
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lepper
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto 606-8501, Japan.
authors.forename: Makoto Mark
authors.initials: MM
authors.lastname: Taketo
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France; Sorbonne Universités, UPMC Université Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, 75013 Paris, France. Electronic address: fabien.le-grand@inserm.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Le Grand
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D017353:Gene Deletion; D018390:Gene Targeting; D018345:Mice, Knockout; D024510:Muscle Development; D009132:Muscles / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D051176:beta Catenin