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Reactive oxygen species enhance differentiation of human embryonic stem cells into mesendodermal lineage

Cited 122 time in Web of Science Cited 126 time in Scopus
Authors

Ji, Ae-Ri; Ku, Seung-Yup; Cho, Myung Soo; Kim, Yoon Young; Oh, Sun Kyung; Moon, Shin Yong; Choi, Young Min; Kim, Seok Hyun; Kim, Yong Jin

Issue Date
2010-03-31
Publisher
KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE; Vol.42 3; 175-186
Keywords
cell differentiationembryonic stem cellsreactive oxygen speciesmitogen-activated protein kinases
Abstract
Recently, reactive oxygen species (ROS) have been studied as a regulator of differentiation into specific cell types in embryonic stem cells (ESCs). However, ROS role in human ESCs (hESCs) is unknown because mouse ESCs have been used mainly for most studies. Herein we suggest that ROS generation may play a critical role in differentiation of hESCs; ROS enhances differentiation of hESCs into bi-potent mesendodermal cell lineage via ROS-involved signaling pathways. In ROS-inducing conditions, expression of pluripotency markers (Oct4, Tra 1-60, Nanog, and Sox2) of hESCs was decreased, while expression of mesodermal and endodermal markers was increased. Moreover, these differentiation events of hESCs in ROS-inducing conditions were decreased by free radical scavenger treatment. hESC-derived embryoid bodies (EBs) also showed similar differentiation patterns by ROS induction. In ROS-related signaling pathway, some of the MAPKs family members in hESCs were also affected by ROS induction. p38 MAPK and AKT (protein kinases B, PKB) were inactivated significantly by buthionine sulfoximine (BSO) treatment. JNK and ERK phosphorylation levels were increased at early time of BSO treatment but not at late time point. Moreover, MAPKs family-specific inhibitors could prevent the mesendodermal differentiation of hESCs by ROS induction. Our results demonstrate that sternness and differentiation of hESCs can be regulated by environmental factors such as ROS.
ISSN
1226-3613
Language
English
URI
https://hdl.handle.net/10371/76826
DOI
https://doi.org/10.3858/emm.2010.42.3.018
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