TY - JOUR
T1 - Metabolic remodelling during early mouse embryo development
AU - Zhao, Jing
AU - Yao, Ke
AU - Yu, Hua
AU - Zhang, Ling
AU - Xu, Yuyan
AU - Chen, Lang
AU - Sun, Zhen
AU - Zhu, Yuqing
AU - Zhang, Cheng
AU - Qian, Yuli
AU - Ji, Shuyan
AU - Pan, Hongru
AU - Zhang, Min
AU - Chen, Jie
AU - Correia, Cristina
AU - Weiskittel, Taylor
AU - Lin, Da Wei
AU - Zhao, Yuzheng
AU - Chandrasekaran, Sriram
AU - Fu, Xudong
AU - Zhang, Dan
AU - Fan, Heng Yu
AU - Xie, Wei
AU - Li, Hu
AU - Hu, Zeping
AU - Zhang, Jin
N1 - Funding Information:
We thank J. Sheng, L. Shen, D. Ye, Y. Ni, X. Huang, M. Guan, Y. Yang, C. Navdeep and A. Intlekofer for helpful discussion and sharing of facilities. We thank G. Daley and M. Teitell for their long-term support. J. Zhang is supported by the National Key Research and Development Program of China (2018YFA0107100). Z.H. is supported by grants from National Natural Science Foundation of China (92057209). J. Zhang is also supported by the National Key Research and Development Program of China (2018YFA0107103 and 2018YFC1005002), the National Natural Science Foundation projects of China (31871453 and 91857116), Zhejiang Innovation Team grant (2019R01004) and the Zhejiang Natural Science Foundation projects of China (LR19C120001). Z.H. is also supported by grants from National Key R&D Program of China (2019YFA0802102), Tsinghua-Peking Center for Life Sciences (100084) and Beijing Frontier Research Center for Biological Structure.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
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U2 - 10.1038/s42255-021-00464-x
DO - 10.1038/s42255-021-00464-x
M3 - Article
C2 - 34650276
AN - SCOPUS:85117250577
SN - 2522-5812
VL - 3
SP - 1372
EP - 1384
JO - Nature Metabolism
JF - Nature Metabolism
IS - 10
ER -