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Optimal ROS Signaling Is Critical for Nuclear Reprogramming.

Gang Zhou1, Shu Meng1, Yanhui Li1

  • 1Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX 77030, USA.

Cell Reports
|April 28, 2016
PubMed
Summary

Reactive oxygen species (ROS) signaling is crucial for efficient nuclear reprogramming. Optimal ROS levels are essential for inducing pluripotency, with both depletion and excess impairing the process.

Keywords:
CRISPR/Cas9NADPH oxidaseNrf2iPSCsnuclear reprogrammingreactive oxygen species

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Area of Science:

  • Cell Biology
  • Stem Cell Research
  • Immunology

Background:

  • Efficient nuclear reprogramming requires innate immunity activation.
  • Innate immune activation involves reactive oxygen species (ROS) signaling.

Purpose of the Study:

  • To investigate the role of ROS signaling in nuclear reprogramming.
  • To examine ROS production during induced pluripotent stem cell (iPSC) generation.

Main Methods:

  • Studied ROS generation in doxycycline-inducible mouse embryonic fibroblasts (MEFs) with Yamanaka factors (OSKM).
  • Assessed reprogramming efficiency after ROS depletion (antioxidants, Nox inhibitors) or p22(phox) manipulation (knockdown/knockout).
  • Evaluated effects of excessive ROS generation.

Main Results:

  • ROS generation significantly increased at the onset of reprogramming.
  • Depleting ROS or inhibiting Nox complex (p22(phox) knockdown/knockout) reduced reprogramming efficiency.
  • Excessive ROS generation impaired reprogramming.

Conclusions:

  • ROS signaling is activated early in nuclear reprogramming.
  • Optimal ROS levels are essential for efficient induction of pluripotency.