美国西奈山伊坎医学院Robert S. Krauss研究团队发现，损伤反应性Rac-Rho GTP酶开关通过快速细胞骨架重塑驱动肌肉干细胞的激活。这一研究成果于2022年5月20日在线发表在国际学术期刊《细胞—干细胞》上。

通过结合体内和体外的方法，研究人员发现，静止的骨骼肌干细胞（MuSC）据有精心设计的、由Rac GTP酶促进的细胞质突起，这会通过Rho/ROCK信号的上调对损伤作出反应，进而促进突起回缩并推动下游的激活事件。这些早期事件涉及快速的细胞骨架重排，并且不依赖于外源性生长因子而发生。这种机制在广泛的造血干细胞激活模型中是保守的，包括损伤、疾病和遗传性静止期的丧失。这些结果重新定义了MuSC的激活，并提出了一个核心机制。即静止的干细胞启动对损伤的反应。

据介绍，许多组织都有静止的干细胞，在受伤时被激活，随后增殖和分化以修复组织损伤。然而，干细胞感知损伤并从静止状态过渡到激活的机制在很大程度上仍是未知的。常驻MuSC是肌肉再生和修复的重要协调者。

附：英文原文

Title: An injury-responsive Rac-to-Rho GTPase switch drives activation of muscle stem cells through rapid cytoskeletal remodeling

Author: Allison P. Kann, Margaret Hung, Wei Wang, Jo Nguyen, Penney M. Gilbert, Zhuhao Wu, Robert S. Krauss

Issue&Volume: 2022-05-20

Abstract: Many tissues harbor quiescent stem cells that are activated upon injury, subsequentlyproliferating and differentiating to repair tissue damage. Mechanisms by which stemcells sense injury and transition from quiescence to activation, however, remain largelyunknown. Resident skeletal muscle stem cells (MuSCs) are essential orchestrators ofmuscle regeneration and repair. Here, with a combination of in vivo and ex vivo approaches, we show that quiescent MuSCs have elaborate, Rac GTPase-promoted cytoplasmicprojections that respond to injury via the upregulation of Rho/ROCK signaling, facilitatingprojection retraction and driving downstream activation events. These early eventsinvolve rapid cytoskeletal rearrangements and occur independently of exogenous growthfactors. This mechanism is conserved across a broad range of MuSC activation models,including injury, disease, and genetic loss of quiescence. Our results redefine MuSCactivation and present a central mechanism by which quiescent stem cells initiateresponses to injury.

DOI: 10.1016/j.stem.2022.04.016

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00169-2