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Role of metabolic regulation in primordial germ cell formation and differentiation

Research Project

Project/Area Number 19K06434
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42030:Animal life science-related
Research InstitutionTohoku 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
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords始原生殖細胞 / 代謝 / エピゲノム / 栄養 / 代謝調節 / エピゲノム制御 / O-GlcNAc / 発生分化
Outline of Research at the Start

本研究は、環境要因を介した代謝調節の変化が、マウス胎仔期の始原生殖細胞の発生・分化にどのような影響を与えるかを包括的に解明することを目的とする。申請者はこれまでに、マウス始原生殖細胞の発生・分化に伴う代謝状態の変化について研究を進めてきたが、どのような代謝化合物・代謝経路がどのような分子メカニズムにより始原生殖細胞の発生・分化を制御するか、は未だ不明な点が多い。そこで本研究では、培養下、様々な環境条件で始原生殖細胞の分化誘導を行い、始原生殖細胞の発生・分化に寄与する代謝系を包括的に特定する。特定した代謝系について、代謝調節が始原生殖細胞の発生・分化を制御する分子メカニズムの解明に取り組む。

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.

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。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020 2019

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] 生殖細胞の代謝特性から「作る」ための栄養環境を考える2023

    • Author(s)
      林陽平
    • Journal Title

      細胞

      Volume: 55 Pages: 30-33

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Metabolic pathways regulating the development and non-genomic heritable traits of germ cells2022

    • Author(s)
      MATSUI Yasuhisa、HAYASHI Yohei
    • Journal Title

      Journal of Reproduction and Development

      Volume: 68 Issue: 2 Pages: 96-103

    • DOI

      10.1262/jrd.2021-137

    • NAID

      130008134310

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SP600125 Enhances Temperature-Controlled Repeated Thermal Stimulation-Induced Neurite Outgrowth in PC12-P1F1 Cells2022

    • Author(s)
      Luo You-Ran、Kudo Tada-aki、Tominami Kanako、Izumi Satoshi、Tanaka Takakuni、Hayashi Yohei、Noguchi Takuya、Matsuzawa Atsushi、Nakai Junichi、Hong Guang、Wang Hang
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 24 Pages: 15602-15602

    • DOI

      10.3390/ijms232415602

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolic Control of Germline Formation and Differentiation in Mammals2022

    • Author(s)
      Hayashi Yohei、Matsui Yasuhisa
    • Journal Title

      Sexual Development

      Volume: 27 Issue: 5-6 Pages: 1-16

    • DOI

      10.1159/000520662

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Beta 2-Adrenergic Receptor Gly16Arg Polymorphism on Taste Preferences in Healthy Young Japanese Adults2022

    • Author(s)
      Narita Kohei、Kudo Tada-aki、Hong Guang、Tominami Kanako、Izumi Satoshi、Hayashi Yohei、Nakai Junichi
    • Journal Title

      Nutrients

      Volume: 14 Issue: 7 Pages: 1430-1430

    • DOI

      10.3390/nu14071430

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Abnormal early folliculogenesis due to impeded pyruvate metabolism in mouse oocytes.2021

    • Author(s)
      Tanaka, K., Hayashi, Y., Takehara, A., Ito-Matsuoka, Y., Tachibana, M., Yaegashi, N., Matsui, Y.
    • Journal Title

      Biology of Reproduction

      Volume: 105 Issue: 1 Pages: 64-75

    • DOI

      10.1093/biolre/ioab064

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proteomic and metabolomic analyses uncover sex-specific regulatory pathways in mouse fetal germline differentiation†2020

    • Author(s)
      Hayashi Yohei、Mori Masaru、Igarashi Kaori、Tanaka Keiko、Takehara Asuka、Ito-Matsuoka Yumi、Kanai Akio、Yaegashi Nobuo、Soga Tomoyoshi、Matsui Yasuhisa
    • Journal Title

      Biology of Reproduction

      Volume: 103 Issue: 4 Pages: 717-735

    • DOI

      10.1093/biolre/ioaa115

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association between Beta3-Adrenergic Receptor Trp64Arg Polymorphism and Fat Preference in Healthy Young Japanese Women2019

    • Author(s)
      Watanabe Kei、Hong Guang、Tominami Kanako、Izumi Satoshi、Hayashi Yohei、Kudo Tada-aki
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 248 Issue: 3 Pages: 181-192

    • DOI

      10.1620/tjem.248.181

    • NAID

      130007683912

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Roles of O-GlcNAcylation in metabolo-epigenetic regulation of germ cell specification2022

    • Author(s)
      林陽平
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Role of serine metabolism in early embryogenesis and epigenetic regulation2022

    • Author(s)
      林陽平
    • Organizer
      生殖細胞・全能性合同国際シンポジウム
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 代謝調節を基盤とした全能期胚エピゲノムの制御とその継続性の解明2022

    • Author(s)
      林陽平
    • Organizer
      全能性自己紹介セミナー
    • Related Report
      2022 Annual Research Report
  • [Presentation] 代謝調節を基盤とした生殖細胞の性スペクトラム2022

    • Author(s)
      林陽平
    • Organizer
      新学術領域研究「性スペクトラム」 第6回領域会議
    • Related Report
      2021 Research-status Report
  • [Presentation] 雌雄に特徴的な代謝系を介した生殖細胞の性スペクトラム制御機構2021

    • Author(s)
      林陽平
    • Organizer
      新学術領域研究「性スペクトラム」 第5回領域会議
    • Related Report
      2021 Research-status Report
  • [Presentation] The role of glucose metabolism in primordial germ cell fate determination2021

    • Author(s)
      林陽平
    • Organizer
      2021年度日本分子生物学会年会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Metabolic control for ensuring integrity in male germline differentiation2020

    • Author(s)
      林陽平
    • Organizer
      第2回配偶子インテグリティ領域会議・若手会議合同集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Metabolic control-based sex spectrum regulation in germ cells2020

    • Author(s)
      林陽平
    • Organizer
      2021年度性スペクトラム領域会議
    • Related Report
      2020 Research-status Report
  • [Presentation] Metabolic control of male germline differentiation and integrity2020

    • Author(s)
      林陽平
    • Organizer
      新学術領域研究合同公開シンポジウム 2020
    • Related Report
      2020 Research-status Report
  • [Presentation] マウス生殖細胞分化における代謝調節の変化とその役割2020

    • Author(s)
      林陽平
    • Organizer
      「世界を先導するリプロダクションコアの形成」研究交流会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Regulation of metabolic signaling in mouse primordial germ cell development2019

    • Author(s)
      Yohei Hayashi
    • Organizer
      Cold Spring Harbor Laboratory Meeting: Metabolic Signaling
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Proteomic and metabolomic characterization in mouse fetal germline differentiation2019

    • Author(s)
      Yohei Hayashi
    • Organizer
      2019年度日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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