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2016 ; 15
(5
): 919-925
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Optimal ROS Signaling Is Critical for Nuclear Reprogramming
#MMPMID27117405
Zhou G
; Meng S
; Li Y
; Ghebre YT
; Cooke JP
Cell Rep
2016[May]; 15
(5
): 919-925
PMID27117405
show ga
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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