Open AccessDominant Role of Peroxiredoxin/JNK Axis in Stemness Regulation During Neurogenesis from Embryonic Stem Cells
Author(s) -
Kim SunUk,
Park YoungHo,
Kim JinMan,
Sun HuNan,
Song InSung,
Huang Song Mei,
Lee SangHee,
Chae JungIl,
Hong Su,
Sik Choi Sung,
Choi SeungCheol,
Lee TaeHoon,
Kang Sang Won,
Rhee Sue Goo,
Chang KyuTae,
Lee Sang Ho,
Yu DaeYeul,
Lee DongSeok
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1593
Subject(s) - neurogenesis , embryonic stem cell , biology , microbiology and biotechnology , stem cell , neural stem cell , peroxiredoxin , reactive oxygen species , kinase , genetics , biochemistry , enzyme , peroxidase , gene
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. S tem C ells 2014;32:998–1011