Zinc Chloride Transiently Maintains Mouse Embryonic Stem Cell Pluripotency by Activating Stat3 Signaling.
Zinc Chloride Transiently Maintains Mouse Embryonic Stem Cell Pluripotency by Activating Stat3 Signaling.
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DOI：
10.1371/journal.pone.0148994
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Cheng J
中科院分区：
文献类型：
--
作者：
Hu J;Yang Z;Wang J;Yu J;Guo J;Liu S;Qian C;Song L;Wu Y;Cheng J
提高对胚胎干细胞多能性维持的了解对于早期胚胎发育和细胞替代治疗的研究具有重要意义，但多能性背后的机制仍不完全清楚。最近的研究结果表明，锌是人类必需的微量元素，在调节各种信号通路和基因表达方面起着至关重要的作用。然而，它在决定ES细胞命运中的作用仍有待进一步探讨。在此，我们证明了2μM氯化锌在体外短暂地维持了小鼠ES细胞的多能性。在白血病抑制因子(LIF)撤除、维甲酸(RA)或类胚体(EB)分化实验中，经2μM氯化锌处理的小鼠ES细胞仍未分化。此外，氯化锌促进了多能基因的表达，抑制了分化基因的表达。进一步的机制研究表明，氯化锌通过促进信号转导和转录激活因子3(STAT3)的磷酸化而瞬时激活信号转导和转录激活因子3(STAT3)信号。抑制STAT3信号通路可消除氯化锌对小鼠ES细胞多能性的影响。综上所述，本研究表明锌在维持小鼠ES细胞的多能性中起着关键作用，同时也是STAT3信号的重要调节因子。
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.