Optimal ROS Signaling Is Critical for Nuclear Reprogramming

Gang Zhou, Shu Meng, Yanhui Li, Yohannes T. Ghebre, John P. Cooke

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Efficient nuclear reprogramming of somatic cells to pluripotency requires activation of innate immunity. Because innate immune activation triggers reactive oxygen species (ROS) signaling, we sought to determine whether there was a role of ROS signaling in nuclear reprogramming. We examined ROS production during the reprogramming of doxycycline (dox)-inducible mouse embryonic fibroblasts (MEFs) carrying the Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc [OSKM]) into induced pluripotent stem cells (iPSCs). ROS generation was substantially increased with the onset of reprogramming. Depletion of ROS via antioxidants or Nox inhibitors substantially decreased reprogramming efficiency. Similarly, both knockdown and knockout of p22phox-a critical subunit of the Nox (1-4) complex-decreased reprogramming efficiency. However, excessive ROS generation using genetic and pharmacological approaches also impaired reprogramming. Overall, our data indicate that ROS signaling is activated early with nuclear reprogramming, and optimal levels of ROS signaling are essential to induce pluripotency. Zhou et al. show that early generation of reactive oxygen species (ROS) is required for nuclear reprogramming of somatic cells to pluripotency. Genetic knockdown and knockout of the oxidative enzyme Nox (1-4), or addition of antioxidants, suppresses reprogramming. The findings provide insight into mechanisms by which pluripotent stem cells may be generated.

Original languageEnglish (US)
Pages (from-to)919-925
Number of pages7
JournalCell Reports
Volume15
Issue number5
DOIs
StatePublished - May 3 2016

Keywords

  • CRISPR/Cas9
  • IPSCs
  • NADPH oxidase
  • Nrf2
  • Nuclear reprogramming
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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