Role of metabolic regulation in primordial germ cell formation and differentiation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: Tohoku University
• Principal Investigator: Hayashi Yohei 東北大学, 加齢医学研究所, 助教 (00588056)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 始原生殖細胞 / 代謝 / エピゲノム / 栄養

Outline of Final Research Achievements

Metabolic regulation is an important upstream regulator of cell function and differentiation, but the metabolic pathways that play a critical role in primordial germ cell fate determination have been unknown. In this study, we showed that glucose is required for primordial germ cell formation through the hexosamine biosynthetic pathway, which branches off from the glycolysis, and that this effect is mediated by epigenetic regulation via O-linked glycosylation of target proteins. Furthermore, we found that a reduction in carbohydrate metabolism due to a carbohydrate-restricted diet in the mother causes suppression of primordial germ cell formation in the embryo. These results indicate that maternal nutritional, metabolic, and epigenetic controls have an important role in the control of germ cell fate decisions of their offspring.

Free Research Field

生殖細胞研究

Academic Significance and Societal Importance of the Research Achievements

生殖細胞系列は、胎仔期の早い段階で多能性幹細胞から分岐して生じ、増殖・移動を経て生殖巣に入り、配偶子へと分化していく。そのため、胎仔の置かれた環境が生殖細胞分化や将来的に生殖機能に影響を与える可能性が高いものの、それを証明した研究はなかった。本研究で、始原生殖細胞が形成される時点での糖質代謝の重要性を明らかにしたことにより、初めて栄養環境と始原生殖細胞形成の関連性が示唆された。このことは培養系や母体の栄養環境により生殖細胞の分化能や生殖機能に影響を与えうる可能性を示しており、非侵襲的な外部環境からの介入による生殖細胞機能の操作へと繋がることが期待される。