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.
Highlights
embryonic stem (ES) cells are derived from early preimplantation embryos and they have two remarkable properties: the ability to differentiate into virtually all types of cells of the adult body, known as pluripotency; and the capacity for unlimited proliferation while maintaining the pluripotent state, known as self-renewal [1]
For retinoic acid (RA) differentiation assay, mouse ES cells were cultured in 6-well plates. 10μM Retinoic acid (Sigma-Aldrich) and ZnCl2 at different final concentrations were added into leukemia inhibitory factor (LIF) withdrawal medium
Ying et al reported that two potent selective small molecule inhibitors, PD0325901 and CHIR99021, which target mitogen-activated protein kinase kinase (Mek) and glycogen synthase kinase-3 (Gsk3), respectively, are sufficient to sustain efficient mouse ES cell self-renewal and pluripotency [10]
Summary
ES cells are derived from early preimplantation embryos and they have two remarkable properties: the ability to differentiate into virtually all types of cells of the adult body, known as pluripotency; and the capacity for unlimited proliferation while maintaining the pluripotent state, known as self-renewal [1]. These characteristics render ES cells a useful and available tool for investigating the molecular and cellular control of embryogenesis and the mechanisms regarding embryonic developmental diseases [2,3,4,5].
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