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Translational regulation of epigenetic factors in spermatogonial stem cells

Research Project

Project/Area Number 19K23831
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0802:Biomedical structure and function and related fields
Research InstitutionYokohama City University

Principal Investigator

KUROHA Kazushige  横浜市立大学, 医学部, 助教 (50580015)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords精子幹細胞 / エピジェネティクス / 翻訳制御
Outline of Research at the Start

精子幹細胞が自己複製能を不可逆的に喪失し、精子形成へ向けて運命決定される一時期において、大規模なゲノム修飾が引き起こされる転換点が存在する。この大規模なゲノム修飾を起こすための鍵となる酵素(Dnmt3aとGLPタンパク質)の増加は、転写ではなく翻訳により制御されることが示唆されている。本研究は、この転換点における翻訳制御の実態を明らかにするため、1) mRNAの核外輸送、2) 全mRNAの翻訳の亢進/脱抑制、3) mRNAの選択的な翻訳の亢進/脱抑制、の可能性について解析する。これにより、精子幹細胞の分化開始機構が明らかになるだけでなく、不妊症の原因解明やその治療への応用も期待される。

Outline of Final Research Achievements

During the time when spermatogonial stem cells loss their stem cell activity, significant epigenetic changes occur in them. It has been suggested that the enzymes involved in the global epigenetic change (hereinafter called “epigenetic factors”) may be upregulated by translational regulation. In this study, we aimed to investigate the translational regulation of epigenetic factors during the stem cell to progenitor transition. We found that 1) translation of the mRNAs encoding epigenetic factors is strongly repressed in spermatogonial stem cells, 2) different mRNA isoforms are expressed during the transition, and 3) mRNAs encoding epigenetic factors are localized in the cytoplasm regardless of the stem cell and differentiating cells, thus mRNA export from nucleus may not be crucial for the upregulation of epigenetic factors.

Academic Significance and Societal Importance of the Research Achievements

ゲノム修飾酵素の翻訳制御は、精子幹細胞から分化細胞の移行に必要なエピジェネティクス制御の上流にあると考えられ、そのメカニズムを理解することで、成体幹細胞に対して広く適用可能な『細胞運命の決定機構』を翻訳制御の視点で明らかにできると考えられる。これを達成することは、再生医療研究に重要なだけでなく、「多細胞生物における様々な種類の細胞がどのように生み出されるのか」といった生物学における根本の問いの解明につながると期待される。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2021 2019

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results)

  • [Journal Article] Tsga8 is required for spermatid morphogenesis and male fertility in mice2021

    • Author(s)
      Kobayashi Yuki、Tomizawa Shin-ichi、Ono Michio、Kuroha Kazushige、Minamizawa Keisuke、Natsume Koji、Dizdarevic Selma、Dockal Ivana、Tanaka Hiromitsu、Kawagoe Tatsukata、Seki Masahide、Suzuki Yutaka、Ogonuki Narumi、Inoue Kimiko、Matoba Shogo、Anastassiadis Konstantinos、Mizuki Nobuhisa、Ogura Atsuo、Ohbo Kazuyuki
    • Journal Title

      Development

      Volume: 148 Issue: 8

    • DOI

      10.1242/dev.196212

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lack of whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (WFDC2) causes neonatal death from respiratory failure in mice.2019

    • Author(s)
      Nakajima K, Ono M, Radovic U, Dizdarevic S, Tomizawa SI, Kuroha K, Nagamatsu G, Hoshi I, Matsunaga R, Shirakawa T, Kurosawa T, Miyazaki Y, Seki M, Suzuki Y, Koseki H, Nakamura M, Suda T, Ohbo K.
    • Journal Title

      Disease Models & Mechanisms

      Volume: 12 Pages: 40139-40139

    • DOI

      10.1242/dmm.040139

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two classes of EF1-family translational GTPases encoded by giant viruses2019

    • Author(s)
      Zinoviev Alexandra、Kuroha Kazushige、Pestova Tatyana V、Hellen Christopher U T
    • Journal Title

      Nucleic Acids Research

      Volume: 47 Issue: 11 Pages: 5761-5776

    • DOI

      10.1093/nar/gkz296

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2019-09-03   Modified: 2022-01-27  

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