SOXF factors regulate murine satellite cell self-renewal and function through inhibition of β-catenin activity
Abstract
Muscle satellite cells are the primary source of stem cells for postnatal skeletal muscle growth and regeneration. Understanding genetic control of satellite cell formation, maintenance, and acquisition of their stem cell properties is on-going, and we have identified SOXF (SOX7, SOX17, SOX18) transcriptional factors as being induced during satellite cell specification. We demonstrate that SOXF factors regulate satellite cell quiescence, self-renewal and differentiation. Moreover, ablation of Sox17 in the muscle lineage impairs postnatal muscle growth and regeneration. We further determine that activities of SOX7, SOX17 and SOX18 overlap during muscle regeneration, with SOXF transcriptional activity requisite. Finally, we show that SOXF factors also control satellite cell expansion and renewal by directly inhibiting the output of β-catenin activity, including inhibition of Ccnd1 and Axin2. Together, our findings identify a key regulatory function of SoxF genes in muscle stem cells via direct transcriptional control and interaction with canonical Wnt/β-catenin signaling.
Data availability
Sequencing data have been deposited in GEO under accession code GSE63860 and previously published in:Gene Expression Profiling of Muscle Stem Cells Identifies Novel Regulators of Postnatal Myogenesis. Alonso-Martin S, Rochat A, Mademtzoglou D, Morais J, de Reyniès A, Auradé F, Chang TH, Zammit PS, Relaix F. Front Cell Dev Biol. 2016 Jun 21;4:58. doi: 10.3389/fcell.2016.00058. eCollection 2016. PMID: 27446912.
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Chronological expression data from mouse skeletal muscle stem cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE63860).
Article and author information
Author details
Funding
Basque Community (BF106.177)
- Sonia Alonso-Martin
Muscular Dystrophy UK
- Peter S Zammit
Medical Research Council
- Peter S Zammit
FSH Society and BIODESIGN (262948-2)
- Peter S Zammit
Deutsche Forschungsgemeinschaft (KFO192 (Sp1152/8-1))
- Despoina Mademtzoglou
Fondation pour la Recherche Médicale (DEQ20130326526)
- Frédéric Relaix
Agence Nationale de la Recherche (ANR-13-BSV1-0011-02)
- Frédéric Relaix
Agence Nationale de la Recherche (ANR-12-BSV1-0038-04)
- Frédéric Relaix
Agence Nationale de la Recherche (ANR-15-CE13-0011-01)
- Frédéric Relaix
Agence Nationale de la Recherche (ANR-15-RHUS-0003)
- Frédéric Relaix
Deutsche Forschungsgemeinschaft (GK 1631)
- Despoina Mademtzoglou
INSERM Avenir Program
- Frédéric Relaix
Association Française contre les Myopathies (TRANSLAMUSCLE 19507)
- Frédéric Relaix
Association Institut de Myologie
- Frédéric Relaix
Labex REVIVE (ANR-10-LABX-73)
- Frédéric Relaix
European Union Sixth and Seventh Framework Program (MYORES and ENDOSTEM # 241440)
- Peter S Zammit
- Frédéric Relaix
Fondation pour la Recherche Médicale (FDT20130928236)
- Frédéric Relaix
Agence Nationale de la Recherche (ANR 11 BSV2 017 02)
- Frédéric Relaix
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Randy Schekman, Howard Hughes Medical Institute, University of California, Berkeley, United States
Ethics
Animal experimentation: All animals were maintained inside a barrier facility and all experiment were performed in accordance with the European and French regulations for animal care and handling (Project No: 01427.03 approved by MESR and File No: 15-018 from the Ethical Committee of Anses/ENVA/UPEC).
Version history
- Received: February 14, 2017
- Accepted: June 7, 2018
- Accepted Manuscript published: June 8, 2018 (version 1)
- Version of Record published: June 27, 2018 (version 2)
Copyright
© 2018, Alonso-Martin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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