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Identification of genes required for spermatogonial stem cell differentiation

Research Project

Project/Area Number 17K15549
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General anatomy (including histology/embryology)
Research InstitutionYokohama City University

Principal Investigator

Tomizawa Shinichi  横浜市立大学, 医学部, 助教 (00704628)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsエピジェネティクス / 生殖細胞 / 幹細胞 / 発生 / 精子幹細胞 / 精子形成 / 分化 / クロマチン / 遺伝子 / ゲノム / 細胞・組織 / 発現制御 / 解剖学
Outline of Final Research Achievements

In this study, we performed genome-wide transcriptome and epigenome analyses to understand the proliferation and differentiation mechanisms of spermatogonial stem cells (SSCs) in mammals. We collected mouse SSCs and progenitor spermatonia from mouse testis and analysed mRNA and DNA methylation status at the single cell level (M&T-seq). We found that SSCs are potentially heterogeneous with subpopulations showing different transcription and methylation status. Furthermore, from histological and histone modification analyses, we found that a histone methyltransferase Kmt2b plays an essential role for SSC differentiation.

Academic Significance and Societal Importance of the Research Achievements

本研究は、正常な精子形成に欠かせない精子幹細胞の増殖・分化を司る分子機構を明らかにするものである。本研究の成果から、精子幹細胞集団の遺伝子発現制御機構に関する重要な知見が得られたと共に、ヒストン修飾酵素の一つであるKmt2bが精子形成に必要な多くの遺伝子の発現を制御し、精子幹細胞分化において重要な役割を担うことが示された。これらは、原因が明らかでない男性不妊症の研究に対して有用な情報を提供すると同時に、組織幹細胞研究分野の今後の発展に貢献することが期待できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 2017 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Kmt2b conveys monovalent and bivalent H3K4me3 in spermatogonial stem cells at germline and embryonic promoters2018

    • Author(s)
      Tomizawa S, Kobayashi Y, Shirakawa T, Watanabe K, Mizoguchi K, Hoshi I, Nakajima K, Nakabayashi J, Singh S, Dahl A, Alexopoulou D, Seki M, Suzuki Y, Royo H, Peters6, A. H.F.M, Anastassiadis K, Stewart A.F. and Ohbo K
    • Journal Title

      Development

      Volume: 145 Issue: 23

    • DOI

      10.1242/dev.169102

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] エピジェネティック機構を介した精子発生制御メカニズム2019

    • Author(s)
      小林裕貴、尾野道男、溝口敬太、夏目幸治、富澤信一、河越龍方、水木信久、小倉淳郎、大保和之
    • Organizer
      第124回日本解剖学会総会全国学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Kmt2b is required for spermatogenic programs through both bivalent and monovalent priming of the spermatogonial stem cell epigenome.2017

    • Author(s)
      Tomizawa S, Kobayashi Y, Shirakawa T, Hoshi I, Nakajima K, Royo H, Nakamura Y, Peters AHFM, Anastassiadis K, Stewart AF, Yoshida S, Ohbo K
    • Organizer
      The International Research Symposium on Regulation of Germ Cell Development in vivo and in vitro
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Kmt2b is required for spermatogenesis through both bivalent and monovalent priming of the spermatogonial stem cell epigenome.2017

    • Author(s)
      Tomizawa S, Kobayashi Y, Shirakawa T, Hoshi I, Nakajima K, Royo H, Peters AHFM, Anastassiadis K, Stewart AF, Ohbo K
    • Organizer
      EMBO conference: Nuclear structure and dynamics
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 横浜市立大学医学部組織学

    • URL

      http://www-user.yokohama-cu.ac.jp/~finemorp/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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