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首页> 外文期刊>Cell metabolism >Transient Activation of Mitoflashes Modulates Nanog at the Early Phase of Somatic Cell Reprogramming
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Transient Activation of Mitoflashes Modulates Nanog at the Early Phase of Somatic Cell Reprogramming

机译：Mitoflash的瞬态激活在体细胞重编程的早期阶段调节Nanog。

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摘要

The mechanisms of somatic cell reprogramming have been revealed at multiple levels. However, the lack of tools to monitor different reactive oxygen species (ROS) has left their distinct signals and roles in reprogramming unknown. We hypothesized that mitochondrial flashes (mitoflashes), recently identified spontaneous bursts of mitochondrial superoxide signaling, play a role in reprogramming. Here we show that the frequency of mitoflashes transiently increases, accompanied by flash amplitude reduction, during the early stages of reprogramming. This transient activation of mitoflashes at the early stage enhances reprogramming, whereas sustained activation impairs reprogramming. The reprogramming-promoting function of mitoflashes occurs via the upregulation of Nanog expression that is associated with decreases in the methylation status of the Nanog promoter through Tet2 occupancy. Together our findings provide a previously unknown role for superoxide signaling mediated epigenetic regulation in cell fate determination.
机译：体细胞重编程的机制已在多个层面揭示。但是，缺乏用于监视不同活性氧（ROS）的工具，其独特的信号和在重编程中的作用尚不清楚。我们假设线粒体闪烁（mitoflash），最近发现自发的线粒体超氧化物信号爆发，在重编程中起作用。在这里，我们显示了在重新编程的早期阶段，线粒体闪光的频率瞬时增加，并伴随着闪光幅度降低。早期的线粒体闪光灯的这种瞬时激活增强了重新编程，而持续的激活则削弱了重新编程。线粒体闪光的重编程促进功能通过Nanog表达的上调而发生，该上调与通过Tet2占据而降低Nanog启动子的甲基化状态有关。在一起，我们的发现为细胞命运确定中超氧化物信号介导的表观遗传调控提供了以前未知的作用。

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