Migration and differentiation of muscle stem cells are coupled by RhoA signalling during regeneration.
Migration and differentiation of muscle stem cells are coupled by RhoA signalling during regeneration.
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作者：
骨骼肌具有高度的再生性，并由一群迁移性成体肌肉干细胞(MuSCs)介导。有效的肌肉再生需要MUSC群体时空调节的反应，以产生足够的肌肉前体细胞，然后在适当的时间分化。对MUSC迁移和细胞命运之间的关系知之甚少，也不清楚迁移细胞所经历的力量如何影响细胞行为。我们已经使用斑马鱼来了解MUSC细胞黏附、行为和体内命运之间的关系。对表达PAX7的MuSCs对躯干肌局灶性损伤做出反应的成像显示，它们通过突起的方式迁移。通过仔细描述它们对损伤的反应行为，我们发现它们采用了一种受RhoA激酶岩石调控的黏附依赖的迁移模式。ROCK活性受损会导致细胞周期基因表达减少，促进再生肌肉的分化。这与局部黏附动力学和迁移的变化有关，揭示了岩石抑制改变了MuSCs与其局部环境的相互作用。我们认为，MUSC的迁移和分化是对RhoA信号介导的环境力量变化做出反应的耦合过程。
Skeletal muscle is highly regenerative and is mediated by a population of migratory adult muscle stem cells (muSCs). Effective muscle regeneration requires a spatio-temporally regulated response of the muSC population to generate sufficient muscle progenitor cells that then differentiate at the appropriate time. The relationship between muSC migration and cell fate is poorly understood and it is not clear how forces experienced by migrating cells affect cell behaviour. We have used zebrafish to understand the relationship between muSC cell adhesion, behaviour and fate in vivo. Imaging of pax7-expressing muSCs as they respond to focal injuries in trunk muscle reveals that they migrate by protrusive-based means. By carefully characterizing their behaviour in response to injury we find that they employ an adhesion-dependent mode of migration that is regulated by the RhoA kinase ROCK. Impaired ROCK activity results in reduced expression of cell cycle genes and increased differentiation in regenerating muscle. This correlates with changes to focal adhesion dynamics and migration, revealing that ROCK inhibition alters the interaction of muSCs to their local environment. We propose that muSC migration and differentiation are coupled processes that respond to changes in force from the environment mediated by RhoA signalling.
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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：
3.7
作者：
Jacob AE;Turner CE;Amack JD
通讯作者：
Amack JD
影响因子：
8
作者：
Fu, Xin;Wang, Huating;Hu, Ping
通讯作者：
Hu, Ping
影响因子：
9.2
作者：
Bachir, Alexia I.;Zareno, Jessica;Moissoglu, Konstadinos;Plow, Edward F.;Gratton, Enrico;Horwitz, Alan R.
通讯作者：
Horwitz, Alan R.
影响因子：
3.4
作者：
Haroon M;Klein-Nulend J;Bakker AD;Jin J;Seddiqi H;Offringa C;de Wit GMJ;Le Grand F;Giordani L;Liu KJ;Knight RD;Jaspers RT
通讯作者：
Jaspers RT