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Publication : Optimal ROS Signaling Is Critical for Nuclear Reprogramming.

First Author  Zhou G Year  2016
Journal  Cell Rep Volume  15
Issue  5 Pages  919-925
PubMed ID  27117405 Mgi Jnum  J:235392
Mgi Id  MGI:5796229 Doi  10.1016/j.celrep.2016.03.084
Citation  Zhou G, et al. (2016) Optimal ROS Signaling Is Critical for Nuclear Reprogramming. Cell Rep 15(5):919-25
abstractText  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 p22(phox)-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.
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