An injury-responsive Rac-to-Rho GTPase switch drives activation of muscle stem cells through rapid cytoskeletal remodeling.
An injury-responsive Rac-to-Rho GTPase switch drives activation of muscle stem cells through rapid cytoskeletal remodeling.
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DOI：
10.1016/j.stem.2022.04.016
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发表时间：
2022-06-02
期刊：
影响因子：
23.9
通讯作者：
Krauss, Robert S.
中科院分区：
文献类型：
--
作者：
Kann, Allison P.;Hung, Margaret;Wang, Wei;Nguyen, Jo;Gilbert, Penney M.;Wu, Zhuhao;Krauss, Robert S.
许多组织含有在损伤时被激活的静止干细胞，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过渡到激活的机制在很大程度上仍然未知。常驻骨骼肌干细胞（MuSC）是肌肉再生和修复的重要协调者。在这里，通过体内和离体方法的组合，我们表明静止的MuSC具有精细的Rac GTP酶促进的细胞质投射，其通过上调Rho/ROCK信号传导对损伤做出反应，促进投射回缩并驱动下游激活事件。这些早期事件涉及快速的细胞骨架重排，并且独立于外源性生长因子发生。这种机制在广泛的MuSC激活模型中是保守的，包括损伤、疾病和遗传性静止丧失。我们的研究结果重新定义了MuSC的激活，并提出了一种静止干细胞启动损伤反应的中心机制。静止的肌肉干细胞（MuSC）在体内具有长的、精细的细胞质突起。在这篇论文中，Kann及其同事确定了一种机制，通过这种机制，MuSC通过一个小的GTdR活性开关打破静止，驱动投射回缩，细胞骨架重排和下游事件对干细胞活化很重要。
Many tissues harbor quiescent stem cells that are activated upon injury, subsequently proliferating and differentiating to repair tissue damage. Mechanisms by which stem cells sense injury and transition from quiescence to activation, however, remain largely unknown. Resident skeletal muscle stem cells (MuSCs) are essential orchestrators of muscle regeneration and repair. Here, with a combination of in vivo and ex vivo approaches, we show that quiescent MuSCs have elaborate, Rac GTPase-promoted cytoplasmic projections that respond to injury via upregulation of Rho/ROCK signaling, facilitating projection retraction and driving downstream activation events. These early events involve rapid cytoskeletal rearrangements and occur independently of exogenous growth factors. This mechanism is conserved across a broad range of MuSC activation models, including injury, disease, and genetic loss of quiescence. Our results redefine MuSC activation and present a central mechanism by which quiescent stem cells initiate responses to injury. Quiescent muscle stem cells (MuSCs) have long, elaborate, cytoplasmic projections in vivo. In this manuscript, Kann and colleagues identify a mechanism by which MuSCs break quiescence through a small GTPase activity switch, driving projection retraction, cytoskeletal rearrangements, and downstream events important for stem cell activation.
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DOI：
10.1083/jcb.201310035
发表时间：
2014-04-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bentzinger CF;von Maltzahn J;Dumont NA;Stark DA;Wang YX;Nhan K;Frenette J;Cornelison DD;Rudnicki MA
通讯作者：
Rudnicki MA
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
DOI：
10.1073/pnas.86.4.1292
发表时间：
1989-02-01
影响因子：
11.1
作者：
CHAPMAN, VM;MILLER, DR;CASKEY, CT
通讯作者：
CASKEY, CT
影响因子：
3.7
作者：
Bhadriraju, Kiran;Yang, Michael;Chen, Christopher S.
通讯作者：
Chen, Christopher S.
影响因子：
4
作者：
Cen, B;Selvaraj, A;Prywes, R
通讯作者：
Prywes, R