Pashkovskaia Natalia, Gey Uta, Rödel Gerhard
Institute of Genetics, Technische Universität Dresden, Dresden 01217, Germany.
Institute of Genetics, Technische Universität Dresden, Dresden 01217, Germany.
Stem Cell Res. 2018 Jul;30:180-191. doi: 10.1016/j.scr.2018.06.007. Epub 2018 Jun 19.
ROS are frequently associated with deleterious effects caused by oxidative stress. Despite the harmful effects of non-specific oxidation, ROS also function as signal transduction molecules that regulate various biological processes, including stem cell proliferation and differentiation. Here we show that mitochondrial ROS level determines cell fate during differentiation of the pluripotent stem cell line P19. As stem cells in general, P19 cells are characterized by a low respiration activity, accompanied by a low level of ROS formation. Nevertheless, we found that P19 cells contain fully assembled mitochondrial electron transport chain supercomplexes (respirasomes), suggesting that low respiration activity may serve as a protective mechanism against ROS. Upon elevated mitochondrial ROS formation, the proliferative potential of P19 cells is decreased due to longer S phase of the cell cycle. Our data show that besides being harmful, mitochondrial ROS production regulates the differentiation potential of P19 cells: elevated mitochondrial ROS level favours trophoblast differentiation, whereas preventing neuron differentiation. Therefore, our results suggest that mitochondrial ROS level serves as an important factor that directs differentiation towards certain cell types while preventing others.
活性氧（ROS）常与氧化应激所造成的有害影响相关联。尽管非特异性氧化具有有害作用，但ROS也作为信号转导分子发挥作用，调节包括干细胞增殖和分化在内的各种生物学过程。在此我们表明，线粒体ROS水平在多能干细胞系P19分化过程中决定细胞命运。作为一般的干细胞，P19细胞的特征在于呼吸活性低，同时ROS生成水平也低。然而，我们发现P19细胞含有完全组装好的线粒体电子传递链超复合物（呼吸体），这表明低呼吸活性可能作为一种针对ROS的保护机制。当线粒体ROS生成增加时，由于细胞周期的S期延长，P19细胞的增殖潜能降低。我们的数据表明，线粒体ROS生成除具有有害作用外，还调节P19细胞的分化潜能：线粒体ROS水平升高有利于滋养层分化，而阻止神经元分化。因此，我们的结果表明，线粒体ROS水平是指导细胞向某些细胞类型分化同时阻止向其他细胞类型分化的重要因素。
