Fibronectin Regulates Wnt7a Signaling and Satellite Cell Expansion
Open accessAbstract
The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis.
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Sdc4 is expressed in SCs and is required for SC activation.
“Syndecan-4 (Sdc4) is expressed in SCs and is required for SC activation21,22, but a role for Sdc4 in myofibers remains elusive.”
From In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche (2021) · cites this paper as [21]
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- Authors
- Bentzinger, C. F., Wang, Y. X., von Maltzahn, J., Soleimani, V. D., Yin, H., & Rudnicki, M. A.
- Affiliations
- University of Ottawa (CA)
- Corresponding author
- Rudnicki, Michael A.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 12
- Issue
- 1
- Pages
- 75-87
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC3539137
- OpenAlex
- W1995527023
- Cited by
- 386
- References
- 70
- Citations by year
- 2026: 22 · 2025: 22 · 2024: 27 · 2023: 26 · 2022: 37 · 2021: 31 · 2020: 37 · 2019: 32 · 2018: 31 · 2017: 24 · 2016: 35 · 2015: 27 · 2014: 14 · 2013: 19 · 2012: 2
- FWCI
- 14.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Stem Cell Network
- National Institute for Health and Care Research
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044031)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- fibronectin, satellite cells, syndecan-4, Frizzled-7, extracellular matrix, stem cell niche, muscle regeneration
- MeSH terms
- Animals, Cells, Cultured, Female, Fibronectins, Male, Protein Binding, Signal Transduction, Satellite Cells, Skeletal Muscle, RNA, Small Interfering, Immunoprecipitation, Wnt Proteins, Mice
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