Vitamin C enhances Nanog expression via activation of the JAK/STAT signaling pathway

Stem Cells. 2014 Jan;32(1):166-76. doi: 10.1002/stem.1523.


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.

Keywords: Embryonic stem cells; Nanog; Pluripotent stem cells; Signaling pathway; Transcription factors; Vitamin C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Growth Processes / drug effects
  • Cells, Cultured
  • Embryonal Carcinoma Stem Cells / cytology
  • Embryonal Carcinoma Stem Cells / drug effects*
  • Embryonal Carcinoma Stem Cells / metabolism
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects*
  • Embryonic Stem Cells / metabolism
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Janus Kinases / metabolism*
  • Mice
  • Nanog Homeobox Protein
  • Phosphorylation
  • Promoter Regions, Genetic
  • STAT2 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Transfection


  • Homeodomain Proteins
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • STAT2 Transcription Factor
  • Stat2 protein, mouse
  • Janus Kinases
  • Ascorbic Acid