Zinc Chloride Transiently Maintains Mouse Embryonic Stem Cell Pluripotency by Activating Stat3 Signaling

PLoS One. 2016 Feb 24;11(2):e0148994. doi: 10.1371/journal.pone.0148994. eCollection 2016.

Abstract

An improved understanding of the pluripotency maintenance of embryonic stem (ES) cells is important for investigations of early embryo development and for cell replacement therapy, but the mechanism behind pluripotency is still incompletely understood. Recent findings show that zinc, an essential trace element in humans, is critically involved in regulating various signaling pathways and genes expression. However, its role in ES cell fate determination remains to be further explored. Here we showed that 2μM zinc chloride (ZnCl2) transiently maintained mouse ES cell pluripotency in vitro. The cultured mouse ES cells remained undifferentiated under 2μM ZnCl2 treatment in leukemia inhibitory factor (LIF) withdrawal, retinoic acid (RA) or embryoid bodies (EBs) differentiation assays. In addition, ZnCl2 increased pluripotency genes expression and inhibited differentiation genes expression. Further mechanistic studies revealed that ZnCl2 transiently activated signal transducers and activators of transcription 3 (Stat3) signaling through promoting Stat3 phosphorylation. Inhibition of Stat3 signaling abrogated the effects of ZnCl2 on mouse ES cell pluripotency. Taken together, this study demonstrated a critical role of zinc in the pluripotency maintenance of mouse ES cells, as well as an important regulator of Stat3 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorides / pharmacology*
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism*
  • Phosphorylation / drug effects
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*
  • Zinc Compounds / pharmacology*

Substances

  • Chlorides
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Zinc Compounds
  • zinc chloride

Grants and funding

Shanghai Committee of Science and Technology, China; Grant No. 15ZR1432600; funding recipient: Liwen Song; URL: http://www.stcsm.gov.cn/. Shanghai Committee of Science and Technology, China; Grant No.15695841100; funding recipient: Jiajing Cheng; URL: http://www.stcsm.gov.cn/. National Natural Science Foundation of China; Grant No.81202045; URL: http://www.nsfc.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.