Transient Activation of Mitoflashes Modulates Nanog at the Early Phase of Somatic Cell Reprogramming
Transient Activation of Mitoflashes Modulates Nanog at the Early Phase of Somatic Cell Reprogramming
复制标题
线粒体闪现的瞬时激活在体细胞重编程的早期阶段调节 Nanog
DOI：
10.1016/j.cmet.2015.10.002
复制
发表时间：
2016-01-12
期刊：
影响因子：
29
通讯作者：
Liu, Xingguo
中科院分区：
文献类型：
--
作者：
Ying, Zhongfu;Chen, Keshi;Liu, Xingguo
体细胞重编程的机制已在多个层面得到揭示。然而，由于缺乏监测不同活性氧（ROS）的工具，使得它们在重编程中的独特信号和作用未知。我们假设，线粒体闪光（mitoflashes），最近发现的线粒体超氧化物信号的自发爆发，在重编程中发挥作用。在这里，我们表明，mitoflashs的频率瞬时增加，伴随着闪光幅度减少，在早期阶段的重编程。这种在早期阶段的线粒体闪光的瞬时激活增强了重编程，而持续的激活损害了重编程。mitoflashs的重编程促进功能通过Nanog表达的上调而发生，这与通过Tet2占据降低Nanog启动子的甲基化状态有关。总之，我们的研究结果提供了一个以前未知的作用，超氧化物信号介导的表观遗传调控细胞命运的决定。
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.