Regulation of cleavage embryo genes upon DRP1 inhibition in mouse embryonic stem cells.

Regulation of cleavage embryo genes upon DRP1 inhibition in mouse embryonic stem cells.
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DOI:
10.3389/fcell.2023.1191797
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发表时间:
2023
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
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--
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动力相关蛋白1(Dynamic-related protein 1,DRP 1)是线粒体分裂的关键蛋白。在这项研究中,我们发现,DRP 1的活性抑制导致小鼠胚胎干细胞(mESCs)中卵裂胚胎基因的水平增加,这可能反映了多能性产生的瞬时全能性状态。该结果表明,mESC中的DRP 1抑制导致获得与2C样状态相似的新表达谱的趋势。同时,我们也注意到在2C样细胞中,糖酵解/糖异生途径及其相关酶表达显著下调,糖酵解关键酶表达也下调。此外,当从卵裂胚基因开始表达的晚期合子开始抑制DRP 1活性时,早期胚胎的发育受到抑制,并且这些卵裂胚基因在晚期2细胞(2C)阶段不能有效地沉默。综上所述,我们的研究结果表明,DRP 1在沉默全能性到多能性转变的卵裂胚基因中起着重要作用。
Dynamic-related protein 1 (DRP1) is a key protein of mitochondrial fission. In this study, we found that inhibition of activity of DRP1 led to increased levels of cleavage embryo genes in mouse embryonic stem cells (mESCs), which might reflect a transient totipotency status derived from pluripotency. This result indicates that DRP1 inhibition in mESCs leads to a tendency to obtain a new expression profile similar to that of the 2C-like state. Meanwhile, we also noticed that the glycolysis/gluconeogenesis pathway and its related enzymes were significantly downregulated, and the key glycolytic enzymes were also downregulated in various 2C-like cells. Moreover, when DRP1 activity was inhibited from the late zygote when cleavage embryo genes started to express, development of early embryos was inhibited, and these cleavage embryo genes failed to be efficiently silenced at the late 2-cell (2C) stage. Taken together, our result shows that DRP1 plays an important role in silencing cleavage embryo genes for totipotency-to-pluripotency transition.
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