Yohei Hayashi

Assistant Professor,Institute of Development, Aging and Cancer, Tohoku University*Profile is at the time of the award.

2020Inamori Research GrantsBiology & Life sciences

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Research topics: Regulatory mechanism of male fetal germ cell differentiation via serine metabolism in mice

Keyword

Summary: Recently, various metabolic pathways have been shown to affect a wide range of gene expression and cell functions through epigenetic regulation including DNA methylation and histone modification, but the contribution of these regulation to germ cell differentiation is unknown. In this study, I especially focus on serine metabolism, which is strongly enhanced in male fetal germ cells, and try to clarify the whole mechanism in which the control of serine metabolism contributes to epigenome-mediated gene expression and regulates male germ cell differentiation.

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I am very honored to be able to promote this research with the grant from the Inamori Foundation. With this encouragement, I will strive for my research every day, aiming to pioneer novel scientific areas.

Outline of Research Achievments

In this study, we aimed to specify the metabolic pathways that play important roles in germ cells, which are formed during the fetal stage and then differentiate into sperm and eggs through characteristic differentiation in males and females, respectively, and to clarify their roles. In recent years, it has been reported that the increase or decrease in the amount of certain metabolites is involved in the regulation of gene expression and the epigenome (marks attached to DNA and histones that regulate gene expression). Therefore, what kind of metabolic pathways are enhanced or inhibited during germ cell differentiation has been an important issue in the regulation of the process, but many of the changes, especially in fetal germ cells, were unknown. In this study, we analyzed in detail the sex differences in the metabolic state of fetal germ cells, and found that tricarboxylic acid cycle and serine metabolism are enhanced in male germ cells, while pyruvate and fatty acid metabolism are enhanced in female germ cells. As a result of further research, we found that the metabolic pathways of amino acids such as serine, glycine, and methionine are totally enhanced in male germ cells, and that interfering with these pathways changes the differentiation and epigenomic status of male germ cells. On the other hand, pyruvate metabolism, which was enhanced in female germ cells, was found to play an important role in follicle formation through the regulation of gene expression, which was reported in the paper.

Hayashi Y, et al. (2020) Proteomic and metabolomic analyses uncover sex-specific regulatory pathways in mouse fetal germline differentiationdagger. Biol Reprod 103(4):717-735. https://doi.org/10.1093/biolre/ioaa115

Tanaka K, et al. (2021) Abnormal early folliculogenesis due to impeded pyruvate metabolism in mouse oocytes. Biol Reprod. https://doi.org/10.1093/biolre/ioab064

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