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Metabolic remodelling during early mouse embryo development
Nature Metabolism ( IF 20.8 ) Pub Date : 2021-10-14 , DOI: 10.1038/s42255-021-00464-x
Jing Zhao 1 , Ke Yao 2 , Hua Yu 1 , Ling Zhang 1, 3 , Yuyan Xu 1 , Lang Chen 1 , Zhen Sun 1 , Yuqing Zhu 1 , Cheng Zhang 3 , Yuli Qian 4 , Shuyan Ji 5 , Hongru Pan 1 , Min Zhang 1 , Jie Chen 1 , Cristina Correia 6 , Taylor Weiskittel 6 , Da-Wei Lin 7 , Yuzheng Zhao 8 , Sriram Chandrasekaran 7 , Xudong Fu 1, 3 , Dan Zhang 4 , Heng-Yu Fan 9 , Wei Xie 5 , Hu Li 6 , Zeping Hu 2 , Jin Zhang 1, 3, 10
Affiliation  

During early mammalian embryogenesis, changes in cell growth and proliferation depend on strict genetic and metabolic instructions. However, our understanding of metabolic reprogramming and its influence on epigenetic regulation in early embryo development remains elusive. Here we show a comprehensive metabolomics profiling of key stages in mouse early development and the two-cell and blastocyst embryos, and we reconstructed the metabolic landscape through the transition from totipotency to pluripotency. Our integrated metabolomics and transcriptomics analysis shows that while two-cell embryos favour methionine, polyamine and glutathione metabolism and stay in a more reductive state, blastocyst embryos have higher metabolites related to the mitochondrial tricarboxylic acid cycle, and present a more oxidative state. Moreover, we identify a reciprocal relationship between α-ketoglutarate (α-KG) and the competitive inhibitor of α-KG-dependent dioxygenases, l-2-hydroxyglutarate (l-2-HG), where two-cell embryos inherited from oocytes and one-cell zygotes display higher l-2-HG, whereas blastocysts show higher α-KG. Lastly, increasing 2-HG availability impedes erasure of global histone methylation markers after fertilization. Together, our data demonstrate dynamic and interconnected metabolic, transcriptional and epigenetic network remodelling during early mouse embryo development.



中文翻译:

小鼠早期胚胎发育过程中的代谢重塑

在早期哺乳动物胚胎发生过程中,细胞生长和增殖的变化取决于严格的遗传和代谢指令。然而,我们对代谢重编程及其对早期胚胎发育表观遗传调控的影响的理解仍然难以捉摸。在这里,我们展示了小鼠早期发育关键阶段以及双细胞胚胎和胚泡胚胎的全面代谢组学分析,并通过从全能性到多能性的转变重建了代谢景观。我们的综合代谢组学和转录组学分析表明,虽然双细胞胚胎有利于甲硫氨酸、多胺和谷胱甘肽代谢并保持在更还原的状态,但胚泡胚胎具有更高的与线粒体三羧酸循环相关的代谢物,并呈现更氧化的状态。而且,l -2-羟基戊二酸 ( l -2-HG),其中从卵母细胞遗传的双细胞胚胎和单细胞受精卵显示更高的l -2-HG,而囊胚显示更高的 α-KG。最后,增加 2-HG 可用性会阻碍受精后全局组蛋白甲基化标记物的擦除。总之,我们的数据展示了小鼠早期胚胎发育过程中动态和相互关联的代谢、转录和表观遗传网络重塑。

更新日期:2021-10-14
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