龛内 Wnt4 控制肌肉干细胞的力学特性和静止状态。
Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells.
机构信息
The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Graduate Program in Bioengineering, University of California, San Francisco, and University of California, Berkeley, San Francisco, CA 94143, USA; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Cell Stem Cell. 2019 Nov 7;25(5):654-665.e4. doi: 10.1016/j.stem.2019.08.007. Epub 2019 Sep 5.
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.
卫星细胞（SCs）在组织稳态时处于休眠状态。维持 SC 静止的特定旁分泌因子和生态位细胞仍不清楚。我们发现肌纤维产生的 Wnt4 通过 RhoA 维持 SC 静止。使用细胞特异性诱导遗传学，我们发现 Wnt4-Rho 信号轴在成年小鼠的组织稳态中限制 SC 的数量和激活。Wnt4 在静止的 SC 中激活 Rho 以维持机械张力，限制在生态位中的运动，并抑制 YAP。在 RhoA 破坏时诱导 YAP 对于 SC 在稳态下的激活是必需的。在损伤的情况下，生态位中 Wnt4 的缺失加速了 SC 的激活和肌肉修复，而 Wnt4 的过表达将 SC 转变为更深层次的静止状态并延迟肌肉修复。总之，SC 池在早期激活过程中经历动态转变，机械特性和细胞骨架信号的变化先于细胞周期进入。
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