251. Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells
- Author
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Xuefeng Sun, Rebecca S. D’Urso, Jonathon M. Muncie, Valerie M. Weaver, Andrew S. Brack, Josef Christensen, and Susan Eliazer
- Subjects
mechano-properties ,RHOA ,Muscle Fibers, Skeletal ,Cell Cycle Proteins ,Inbred C57BL ,Regenerative Medicine ,Microscopy, Atomic Force ,Medical and Health Sciences ,Transgenic ,Mice ,0302 clinical medicine ,non-canonical ,Wnt4 Protein ,WNT4 ,Stem Cell Niche ,Cytoskeleton ,muscle stem cell ,Tissue homeostasis ,Oligonucleotide Array Sequence Analysis ,Microscopy ,0303 health sciences ,biology ,Adaptor Proteins ,Atomic Force ,Skeletal ,Biological Sciences ,Cell biology ,Satellite Cells ,niche ,Muscle ,Molecular Medicine ,Stem Cell Research - Nonembryonic - Non-Human ,Stem cell ,Signal Transduction ,animal structures ,Skeletal Muscle ,Satellite Cells, Skeletal Muscle ,Context (language use) ,Mice, Transgenic ,Muscle Fibers ,Article ,03 medical and health sciences ,Paracrine signalling ,cell mechanics ,Rho ,Genetics ,Animals ,Regeneration ,quiescence ,Muscle, Skeletal ,030304 developmental biology ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Signal Transducing ,YAP-Signaling Proteins ,Cell Biology ,Stem Cell Research ,Mice, Inbred C57BL ,biology.protein ,Wnt4 ,rhoA GTP-Binding Protein ,030217 neurology & neurosurgery ,Homeostasis ,Developmental Biology - Abstract
Summary Satellite cells (SCs) reside in a dormant state during tissue homeostasis. The specific paracrine agents and niche cells that maintain SC quiescence remain unknown. We find that Wnt4 produced by the muscle fiber maintains SC quiescence through RhoA. Using cell-specific inducible genetics, we find that a Wnt4-Rho signaling axis constrains SC numbers and activation during tissue homeostasis in adult mice. Wnt4 activates Rho in quiescent SCs to maintain mechanical strain, restrict movement in the niche, and repress YAP. The induction of YAP upon disruption of RhoA is essential for SC activation under homeostasis. In the context of injury, the loss of Wnt4 from the niche accelerates SC activation and muscle repair, whereas overexpression of Wnt4 transitions SCs into a deeper state of quiescence and delays muscle repair. In conclusion, the SC pool undergoes dynamic transitions during early activation with changes in mechano-properties and cytoskeleton signaling preceding cell-cycle entry.
- Published
- 2018