
Vitamin C Enhances Nanog Expression Via Activation of the JAK/STAT Signaling Pathway
Author(s) -
Wu Haibo,
Wu Yongyan,
Ai Zhiying,
Yang Liping,
Gao Yuan,
Du Juan,
Guo Zekun,
Zhang Yong
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.1523
Subject(s) - homeobox protein nanog , stat2 , biology , retinoic acid , signal transduction , microbiology and biotechnology , gene knockdown , transactivation , transcription factor , stat protein , rex1 , phosphorylation , ascorbic acid , chromatin immunoprecipitation , cellular differentiation , stat3 , embryonic stem cell , biochemistry , gene expression , promoter , apoptosis , food science , adult stem cell , induced pluripotent stem cell , gene
Vitamin C (Vc), also known as ascorbic acid, is involved in many important metabolic and physiological reactions in the body. Here, we report that Vc enhances the expression of Nanog and inhibits retinoic acid‐induced differentiation of embryonic stem cells. We investigated Vc regulation of Nanog through Janus kinase/signal transducer and activator of transcription pathway using cell signaling pathway profiling systems, and further confirmed by specific pathway inhibition. Using overexpression and knockdown strategies, we demonstrated that STAT2 is a new positive regulator of Nanog and is activated by phosphorylation following Vc treatment. In addition, site mutation analysis identified that STAT2 physically occupies the Nanog promoter, which was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift assays. Taken together, our data suggest a role for Vc in Nanog regulation networks and reveal a novel role for STAT2 in regulating Nanog expression. S tem C ells 2014;32:166–176