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Wnt4调控肌肉干细胞的机械特性与静止状态
作者:小柯机器人 发布时间:2019/9/6 15:19:00

美国加州大学旧金山分校Andrew S. Brack研究组近期发现,细胞微环境中的Wnt4调控肌肉干细胞的机械特性与静止状态。2019年9月5日,《细胞—干细胞》在线发表了这项成果。

研究人员发现由肌纤维产生的Wnt4蛋白通过RhoA维持卫星细胞(SC)静止。使用细胞特异性诱导遗传学,研究人员发现Wnt4-Rho信号轴限制成年小鼠组织稳态期间的SC数量和激活。Wnt4激活静息SC中的Rho以维持机械应变,限制细胞未环境中的运动,并抑制YAP信号。在破坏RhoA时诱导YAP信号对于体内平衡下的SC活化是必需的。在损伤的情况下,细胞微环境Wnt4的丧失加速SC活化和肌肉修复,而Wnt4的过表达将SC转变为更深的静止状态并延迟肌肉修复。总之,SC群体在早期激活期间经历动态转变,即机械特性和细胞骨架信号传导在细胞周期进入之前发生变化。

据介绍,SC在组织稳态期间处于休眠状态。维持SC静止的特异性旁分泌蛋白和微环境细胞仍然未知。

附:英文原文

Title: Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells

Author: Susan Eliazer, Jonathon M. Muncie, Josef Christensen, Xuefeng Sun, Rebecca S. D’Urso, Valerie M. Weaver, Andrew S. Brack

Issue&Volume: 5 September 2019

Abstract: 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.

DOI: 10.1016/j.stem.2019.08.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30342-X

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx