Dominant role of peroxiredoxin/JNK axis in stemness regulation during neurogenesis from embryonic stem cells.
Redox balance has been suggested as an important determinant of "stemness" in embryonic stem cells (ESCs). In this study, we demonstrate that peroxiredoxin (Prx) plays a pivotal role in maintenance of ESC stemness during neurogenesis through suppression of reactive oxygen species (ROS)-sensitive signaling. During neurogenesis, Prx I and Oct4 are expressed in a mutually dependent manner and their expression is abruptly downregulated by an excess of ROS. Thus, in Prx I(-/-) or Prx II(-/-) ESCs, rapid loss of stemness can occur due to spontaneous ROS overload, leading to their active commitment into neurons; however, stemness is restored by the addition of an antioxidant or an inhibitor of c-Jun N-terminal kinase (JNK). In addition, Prx I and Prx II appear to have a tight association with the mechanism underlying the protection of ESC stemness in developing teratomas. These results suggest that Prx functions as a protector of ESC stemness by opposing ROS/JNK cascades during neurogenesis. Therefore, our findings have important implications for understanding of maintenance of ESC stemness through involvement of antioxidant enzymes and may lead to development of an alternative stem cell-based therapeutic strategy for production of high-quality neurons in large quantity.
Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Republic of Korea; National Primate Research Center, KRIBB, Chungcheongbuk-do, Republic of Korea; Division of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Sun-Uk
SU
Kim
Young-Ho
YH
Park
Jin-Man
JM
Kim
Hu-Nan
HN
Sun
In-Sung
IS
Song
Song Mei
SM
Huang
Sang-Hee
SH
Lee
Jung-Il
JI
Chae
Su
S
Hong
Sung
S
Sik Choi
Seung-Cheol
SC
Choi
Tae-Hoon
TH
Lee
Sang Won
SW
Kang
Sue Goo
SG
Rhee
Kyu-Tae
KT
Chang
Sang Ho
SH
Lee
Dae-Yeul
DY
Yu
Dong-Seok
DS
Lee
D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D054464:Peroxiredoxins; C489899:Prdx1 protein, mouse; D048670:MAP Kinase Kinase 4
Antioxidants; Embryonic stem cells; Neurogenesis; Peroxiredoxin; Reactive oxygen species