Metabolic remodelling during early mouse embryo development

Jing Zhao, Ke Yao, Hua Yu, Ling Zhang, Yuyan Xu, Lang Chen, Zhen Sun, Yuqing Zhu, Cheng Zhang, Yuli Qian, Shuyan Ji, Hongru Pan, Min Zhang, Jie Chen, Cristina Correia, Taylor Weiskittel, Da Wei Lin, Yuzheng Zhao, Sriram Chandrasekaran, Xudong FuDan Zhang, Heng Yu Fan, Wei Xie, Hu Li, Zeping Hu, Jin Zhang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1372-1384
Number of pages13
JournalNature Metabolism
Volume3
Issue number10
DOIs
StatePublished - Oct 2021
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology
  • Physiology (medical)

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