Elsevier

Stem Cell Research

Volume 30, July 2018, Pages 180-191
Stem Cell Research

Mitochondrial ROS direct the differentiation of murine pluripotent P19 cells

https://doi.org/10.1016/j.scr.2018.06.007Get rights and content
Under a Creative Commons license
open access

Highlights

  • P19 cells contain functional units of cellular respiration – respirasomes

  • Mitochondrial oxidative metabolism is activated during differentiation of P19 cells.

  • Increased ROS production reduces the proliferative potential of P19 cells.

  • Elevated mitochondrial ROS level favours trophoblast differentiation.

  • Myxothiazol increases expression of genes that regulate trophectoderm formation.

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

Pluripotent stem cell
Differentiation
ROS
Mitochondria electron transport chain supercomplex
Neuron differentiation
Trophoblast differentiation

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