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Interplay between epigenetics and metabolism in transgenerational inheritance

Research Project

Project/Area Number 21H02383
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42030:Animal life science-related
Research InstitutionTokyo University of Science

Principal Investigator

Maezawa So  東京理科大学, 創域理工学部生命生物科学科, 准教授 (90548174)

Co-Investigator(Kenkyū-buntansha) 林 陽平  東北大学, 加齢医学研究所, 助教 (00588056)
大我 政敏  麻布大学, 獣医学部, 講師 (40644886)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords精子形成 / エピジェネティクス / 代謝 / 生殖細胞 / 生殖科学 / エピゲノム / メタボローム / 発生 / 分化 / 発生分化 / 栄養
Outline of Research at the Start

生殖細胞は生命の永続性を担う。生殖細胞が作られる段階で生じた環境変化の影響は、エピゲノムを介して次世代へ受け継がれていく。このようなエピゲノムの世代を超えた伝達は、次世代やその先の世代の発生や行動に影響を与えると考えられているが、その詳細なメカニズムは不明である。本研究では、哺乳類精子形成期に焦点を当て、精子形成期に亘る代謝システムを明らかにするとともに、その時期に構築される配偶子特異的なエピゲノムとの関連性を明らかにする。さらに、栄養環境変化によってもたらされるエピゲノム異常が、次世代の発生に与える影響を明らかにする。本研究成果により、新たな予防医療や健康科学分野の創生につながる。

Outline of Final Research Achievements

A father’s diet can have a significant effect on the future health of his offspring. Although metabolites in spermatogenesis can alter the epigenome in sperm, it remains unclear what and how the nutrient condition affects the germline epigenome established in spermatogenesis. Here we aimed to understand the metabolome dynamics in spermatogenesis. We conducted integrated transcriptomic, proteomic, and metabolomic analyses of male germ cells in mouse spermatogenesis and demonstrated differentiation stage-dependent changes in these processes. We observed that SGOC pathway is consistently upregulated in spermatogonia and spermatocytes, suggesting their involvement in epigenetic changes preceding in males. We further demonstrated that SGOC is important for the progression of spermatogenesis through the establishment of H3K4me1. Our findings shed light on the unrevealed mechanisms of the metabolism-epigenome crosstalk in spermatogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究により、マウス精子形成期において代謝状態が変化すること、さらに代謝状態がエピゲノム形成へ影響を与えることを見出した。今後、精子形成を司る代謝調節システムや、代謝産物がエピゲノム制御に与える分子機構を明らかにすることにより、精子形成に重要な栄養環境の解明に繋がり、将来的に生体外精子形成技術などの再生医学への貢献が期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (18 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 11 results,  Open Access: 7 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] UC Davis/CCHMC(米国)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] PRC1 directs PRC2-H3K27me3 deposition to shield adult spermatogonial stem cells from differentiation2023

    • Author(s)
      Hu Mengwen、Yeh Yu-Han、Maezawa So、Nakagawa Toshinori、Yoshida Shosei、Namekawa Satoshi?H
    • Journal Title

      Nucleic Acids Research

      Volume: 52 Issue: 5 Pages: 2306-2322

    • DOI

      10.1093/nar/gkad1203

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline2023

    • Author(s)
      Kitamura Yuka、Takahashi Kazuki、Maezawa So、Munakata Yasuhisa、Sakashita Akihiko、Kaplan Noam、Namekawa Satoshi H.
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2023.11.30.569508

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] KRAB-zinc-finger proteins regulate endogenous retroviruses to sculpt germline transcriptomes and genome evolution2023

    • Author(s)
      Otsuka Kai、Sakashita Akihiko、Maezawa So、Schultz Richard M.、Namekawa Satoshi H.
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2023.06.24.546405

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PRC1 suppresses a female gene regulatory network to ensure testicular differentiation2023

    • Author(s)
      Maezawa So、Yukawa Masashi、Hasegawa Kazuteru、Sugiyama Ryo、Iizuka Mizuho、Hu Mengwen、Sakashita Akihiko、Vidal Miguel、Koseki Haruhiko、Barski Artem、DeFalco Tony、Namekawa Satoshi H.
    • Journal Title

      Cell Death & Disease

      Volume: 14 Issue: 8

    • DOI

      10.1038/s41419-023-05996-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin2023

    • Author(s)
      Sakashita Akihiko、Ooga Masatoshi、Otsuka Kai、Maezawa So、Takeuchi Chikara、Wakayama Sayaka、Wakayama Teruhiko、Namekawa Satoshi?H
    • Journal Title

      Nucleic Acids Research

      Volume: 51 Issue: 13 Pages: 6668-6683

    • DOI

      10.1093/nar/gkad479

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin2023

    • Author(s)
      *Sakashita A, Ooga M, Otsuka K, Maezawa S, Takeuchi C, Wakayama S, Wakayama T, and *Namekawa SH
    • Journal Title

      Nucleic Acids Research

      Volume: in press

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bioinformatics Pipelines for Identification of Super-Enhancers and 3D Chromatin Contacts2022

    • Author(s)
      Sakashita Akihiko、Takeuchi Chikara、Maezawa So、Namekawa Satoshi H.
    • Journal Title

      Methods Mol. Biol.

      Volume: 2577 Pages: 123-146

    • DOI

      10.1007/978-1-0716-2724-2_9

    • ISBN
      9781071627235, 9781071627242
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ATAC-Seq Analysis of Accessible Chromatin: From Experimental Steps to Data Analysis2022

    • Author(s)
      Tatara Mayu、Ikeda Taiyo、Namekawa Satoshi H.、Maezawa So
    • Journal Title

      Methods Mol. Biol.

      Volume: 2577 Pages: 65-81

    • DOI

      10.1007/978-1-0716-2724-2_5

    • ISBN
      9781071627235, 9781071627242
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] PRC1-mediated epigenetic programming is required to generate the ovarian reserve2022

    • Author(s)
      Hu Mengwen、Yeh Yu-Han、Munakata Yasuhisa、Abe Hironori、Sakashita Akihiko、Maezawa So、Vidal Miguel、Koseki Haruhiko、Hunter Neil、Schultz Richard M.、Namekawa Satoshi H.
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1

    • DOI

      10.1038/s41467-022-31759-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Use of Visual Information by Ant Species Occurring in Similar Urban Anthropogenic Environments2022

    • Author(s)
      Notomi Yusuke、Kazawa Tomoki、Maezawa So、Kanzaki Ryohei、Haupt Stephan Shuichi
    • Journal Title

      Zoological Science

      Volume: 39 Issue: 6 Pages: 529-544

    • DOI

      10.2108/zs220035

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Meiotic sex chromosome inactivation and the XY body: a phase separation hypothesis2021

    • Author(s)
      Alavattam Kris G.、Maezawa So、Andreassen Paul R.、Namekawa Satoshi H.
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 79 Issue: 1

    • DOI

      10.1007/s00018-021-04075-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] マウス精子形成期におけるエピゲノムおよびクロマチン制御機構2023

    • Author(s)
      前澤創
    • Organizer
      第3回有性生殖研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 生命の連続性を担う、生殖細胞のエピゲノム形成機構2022

    • Author(s)
      前澤創
    • Organizer
      日本医科大学・東京理科大学 第9回合同シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Polycomb suppresses a female gene regulatory network in Sertoli cells2022

    • Author(s)
      前澤創
    • Organizer
      第15回日本エピジェネティクス研究会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Dynamic nuclear lamina-chromatin interactions during spermatogenesis2022

    • Author(s)
      前澤創
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Dynamic nuclear lamina-chromatin interactions during spermatogenesis2022

    • Author(s)
      前澤創
    • Organizer
      The International Symposium "Totipotency and Germ Cell Development"
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 生殖細胞ができるメカニズムを明らかに

    • URL

      https://dept.tus.ac.jp/st/teachers/1617/

    • Related Report
      2022 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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