Mitochondrial ROS direct the differentiation of murine pluripotent P19 cells

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Pages (from-to)180-191
Number of pages12
JournalStem cell research
Publication statusPublished - Jul 2018

External IDs

Scopus 85048985912



  • Animals, Cell Differentiation, Cell Proliferation, Mice, Mitochondria/metabolism, Pluripotent Stem Cells/metabolism, Reactive Oxygen Species/metabolism