title: CCAAT/enhancer binding protein β is required for satellite cell self-renewal.
abstract: Postnatal growth and repair of skeletal muscle relies upon a population of quiescent muscle precursor cells, called satellite cells that can be activated to proliferate and differentiate into new myofibers, as well as self-renew to replenish the satellite cell population. The balance between differentiation and self-renewal is critical to maintain muscle tissue homeostasis, and alterations in this equilibrium can lead to chronic muscle degeneration. The transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is expressed in Pax7+satellite cells of healthy muscle and is downregulated during myoblast differentiation. Persistent expression of C/EBPβ upregulates Pax7, inhibits MyoD, and blocks myogenic differentiation.
  
  
  
  Using genetic tools to conditionally abrogate C/EBPβ expression in Pax7+cells, we examined the role of C/EBPβ in self-renewal of satellite cells during muscle regeneration.
  
  
  
  We find that loss of C/EBPβ leads to precocious differentiation at the expense of self-renewal in primary myoblast and myofiber cultures. After a single muscle injury, C/EBPβ-deficient satellite cells fail to self-renew resulting in a reduction of satellite cells available for future rounds of regeneration. After a second round of injury, muscle regeneration is impaired in C/EBPβ conditional knockout mice compared to wild-type control mice. We find that C/EBPβ can regulate Notch2 expression and that restoration of Notch activity in myoblasts lacking C/EBPβ prevents precocious differentiation.
  
  
  
  These findings demonstrate that C/EBPβ is a novel regulator of satellite cell self-renewal during muscle regeneration acting at least in part through Notch2.
authors.affiliation: Graduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.
authors.forename: Neena
authors.initials: N
authors.lastname: Lala-Tabbert
authors.affiliation: Graduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.
authors.forename: Hamood
authors.initials: H
authors.lastname: AlSudais
authors.affiliation: Graduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Marchildon
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.
authors.forename: Dechen
authors.initials: D
authors.lastname: Fu
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada. Nadine.WiperBergeron@uottawa.ca.
authors.forename: Nadine
authors.identifier: 0000-0001-8448-3246
authors.initials: N
authors.lastname: Wiper-Bergeron
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D051379:Mice; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D051883:Receptor, Notch2
keywords: C/EBPβ; MyoD; Notch; Pax7; Satellite cell; Self-renewal