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.
-
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.
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).
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.
Metrics
-
- 2,045
- views
-
- 335
- downloads
-
- 16
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Cell Biology
- Developmental Biology
In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronized sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.
-
- Developmental Biology
The morphogen FGF8 establishes graded positional cues imparting regional cellular responses via modulation of early target genes. The roles of FGF signaling and its effector genes remain poorly characterized in human experimental models mimicking early fetal telencephalic development. We used hiPSC-derived cerebral organoids as an in vitro platform to investigate the effect of FGF8 signaling on neural identity and differentiation. We found that FGF8 treatment increases cellular heterogeneity, leading to distinct telencephalic and mesencephalic-like domains that co-develop in multi-regional organoids. Within telencephalic regions, FGF8 affects the anteroposterior and dorsoventral identity of neural progenitors and the balance between GABAergic and glutamatergic neurons, thus impacting spontaneous neuronal network activity. Moreover, FGF8 efficiently modulates key regulators responsible for several human neurodevelopmental disorders. Overall, our results show that FGF8 signaling is directly involved in both regional patterning and cellular diversity in human cerebral organoids and in modulating genes associated with normal and pathological neural development.