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Metabolic remodelling during early mouse embryo development.

Jing Zhao1, Ke Yao2, Hua Yu1

  • 1Center 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.

Nature Metabolism
|October 15, 2021
PubMed
Summary
This summary is machine-generated.

Early mouse embryo development involves dynamic metabolic shifts, impacting cell states and epigenetic marks. Changes in key metabolites like alpha-ketoglutarate influence histone methylation erasure during this critical transition.

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Area of Science:

  • Developmental Biology
  • Metabolomics
  • Epigenetics

Background:

  • Cell growth and proliferation in early mammalian embryogenesis are guided by genetic and metabolic cues.
  • Metabolic reprogramming's role in early embryonic epigenetic regulation is not fully understood.

Purpose of the Study:

  • To comprehensively profile metabolites during key stages of mouse early development.
  • To elucidate the metabolic landscape and its connection to epigenetic changes from totipotency to pluripotency.

Main Methods:

  • Integrated metabolomics and transcriptomics profiling of mouse embryos at two-cell and blastocyst stages.
  • Analysis of metabolic pathways including methionine, polyamine, glutathione, and the tricarboxylic acid cycle.
  • Investigation of alpha-ketoglutarate (α-KG) and L-2-hydroxyglutarate (L-2-HG) levels and their impact on histone methylation.

Main Results:

  • Two-cell embryos exhibit higher L-2-hydroxyglutarate (L-2-HG) and favor reductive metabolic states (methionine, polyamine, glutathione metabolism).
  • Blastocyst embryos show higher alpha-ketoglutarate (α-KG) and are in a more oxidative state, with increased tricarboxylic acid cycle metabolites.
  • Elevated L-2-HG levels were found to inhibit the erasure of global histone methylation markers post-fertilization.

Conclusions:

  • Early mouse embryo development involves dynamic metabolic, transcriptional, and epigenetic network remodeling.
  • A reciprocal relationship between α-KG and L-2-HG is identified, influencing epigenetic reprogramming.
  • Metabolic state is intricately linked to the epigenetic modifications essential for developmental transitions.