![]() ![]() Together, our data demonstrate dynamic and interconnected metabolic, transcriptional and epigenetic network remodelling during early mouse embryo development. Lastly, increasing 2-HG availability impedes erasure of global histone methylation markers after fertilization. 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. 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. 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. ![]() However, our understanding of metabolic reprogramming and its influence on epigenetic regulation in early embryo development remains elusive. early mammalian embryogenesis, changes in cell growth and proliferation depend on strict genetic and metabolic instructions. 13 Institute of Hematology, Zhejiang University, Hangzhou, China. 12 Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China. 11 Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University, Hangzhou, China. 10 School of Pharmaceutical Sciences, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China.1 Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University, Hangzhou, China. 9 Life Sciences Institute, Zhejiang University, Hangzhou, China.8 Optogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Research Unit of Chinese Academy of Medical Sciences, East China University of Science and Technology, Shanghai, China.7 Center of Computational Medicine and Bioinformatics, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.6 Center for Individualized Medicine, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, NY, USA.5 Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.4 Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.3 Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China.2 School of Pharmaceutical Sciences, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China.1 Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University, Hangzhou, China. ![]()
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