Fibronectin Regulates Wnt7a Signaling and Satellite Cell Expansion

• Published in: Cell stem cell Vol. 12; no. 1; pp. 75 - 87
• Main Authors: Bentzinger, C. Florian, Wang, Yu Xin, von Maltzahn, Julia, Soleimani, Vahab D., Yin, Hang, Rudnicki, Michael A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.01.2013
• Subjects: Animals; Cells, Cultured; extracellular matrix; Female; fibronectins; Fibronectins - genetics; Fibronectins - metabolism; glycoproteins; Immunoprecipitation; Male; Mice; muscle development; muscles; Protein Binding; RNA, Small Interfering; Satellite Cells, Skeletal Muscle - cytology; Satellite Cells, Skeletal Muscle - metabolism; Signal Transduction - genetics; Signal Transduction - physiology; stem cells; Wnt Proteins - genetics; Wnt Proteins - metabolism
• ISSN: 1934-5909; 1875-9777; 1875-9777
• DOI: 10.1016/j.stem.2012.09.015

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. [Display omitted] ► Fzd7 and Sdc4 form a coreceptor complex in satellite cells ► FN stimulates Wnt7a activity through the Fzd7/Sdc4 coreceptor complex ► Activating satellite cells remodel their niche with FN ► FN regulates the satellite cell pool during muscle regeneration Activated satellite cells remodel their niche by upregulating Fibronectin, which stimulates Wnt7a to induce their symmetric expansion.