Mitochondrial ROS direct the differentiation of murine pluripotent P19 cells

Stem Cell Res. 2018 Jul:30:180-191. doi: 10.1016/j.scr.2018.06.007. Epub 2018 Jun 19.

Abstract

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.

Keywords: Differentiation; Mitochondria electron transport chain supercomplex; Neuron differentiation; Pluripotent stem cell; ROS; Trophoblast differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Reactive Oxygen Species