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CCAAT/enhancer binding protein β is required for satellite cell self-renewal.
Skelet Muscle. 2016 12 07; 6(1):40.SM

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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+Show Affiliations

Graduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.Graduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.Graduate Program in Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada. Nadine.WiperBergeron@uottawa.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27923399

Citation

Lala-Tabbert, Neena, et al. "CCAAT/enhancer Binding Protein Β Is Required for Satellite Cell Self-renewal." Skeletal Muscle, vol. 6, no. 1, 2016, p. 40.
Lala-Tabbert N, AlSudais H, Marchildon F, et al. CCAAT/enhancer binding protein β is required for satellite cell self-renewal. Skelet Muscle. 2016;6(1):40.
Lala-Tabbert, N., AlSudais, H., Marchildon, F., Fu, D., & Wiper-Bergeron, N. (2016). CCAAT/enhancer binding protein β is required for satellite cell self-renewal. Skeletal Muscle, 6(1), 40.
Lala-Tabbert N, et al. CCAAT/enhancer Binding Protein Β Is Required for Satellite Cell Self-renewal. Skelet Muscle. 2016 12 7;6(1):40. PubMed PMID: 27923399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CCAAT/enhancer binding protein β is required for satellite cell self-renewal. AU - Lala-Tabbert,Neena, AU - AlSudais,Hamood, AU - Marchildon,François, AU - Fu,Dechen, AU - Wiper-Bergeron,Nadine, Y1 - 2016/12/07/ PY - 2016/07/13/received PY - 2016/11/08/accepted PY - 2016/12/8/entrez PY - 2016/12/8/pubmed PY - 2018/2/2/medline KW - C/EBPβ KW - MyoD KW - Notch KW - Pax7 KW - Satellite cell KW - Self-renewal SP - 40 EP - 40 JF - Skeletal muscle JO - Skelet Muscle VL - 6 IS - 1 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 2044-5040 UR - https://www.unboundmedicine.com/medline/citation/27923399/CCAAT/enhancer_binding_protein_β_is_required_for_satellite_cell_self_renewal_ L2 - https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-016-0112-8 DB - PRIME DP - Unbound Medicine ER -