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The histone demethylase FBXL10 regulates the proliferation of spermatogonia and ensures long-term sustainable spermatogenesis in mice

Research Project

Project/Area Number 25860157
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionThe University of Tokyo

Principal Investigator

Manabu Ozawa  東京大学, 医科学研究所, 助教 (80608787)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords精子形成 / 細胞周期 / 生殖細胞 / エピジェネティクス / 精巣
Outline of Final Research Achievements

In this study, we show the important roles of FBXL10 as a histone demethylase in sustainable sperm production using mice in which the JmjC domain of Fbxl10 was deleted (Fbxl10 KO). In histological analysis, testes from 7-month-old Fbxl10 KO mice contained a greater ratio of seminiferous tubules exhibiting degeneration of spermatogenesis. Further analysis using an in vitro spermatogonia culture system (germline stem cells (GSCs)) revealed that Fbxl10 KO GSCs expressed a significantly higher level of P21 and P19 mRNA than wild-type (WT) GSCs. Furthermore, the doubling speed of Fbxl10 KO GSCs was significantly slower than that of WT GSCs. In addition, an in vivo study indicated that recovery of spermatogenesis after a transient reduction in the number of testicular germ cells by busulfan treatment was significantly slower in Fbxl10 KO mice than in WT mice. These data suggest that Fbxl10 plays important roles in long-term sustainable spermatogenesis via regulating cell cycle.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (11 results)

All 2016 2015 2014 2013

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

  • [Journal Article] The histone demethylase FBXL10 regulates the proliferation of spermatogonia and ensures long-term sustainable spermatogenesis in mice2016

    • Author(s)
      Ozawa M, Fukuda T, Nakamoto R, Honda H, Yoshida N
    • Journal Title

      Biology of Reproduction

      Volume: 94 Issue: 4 Pages: 1-11

    • DOI

      10.1095/biolreprod.115.135988

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The histone demethylase Fbxl11/Kdm2a plays an essential role in embryonic development by repressing cell-cycle regulators2015

    • Author(s)
      Kawakami E, Tokunaga A, Ozawa M, Sakamoto R, Yoshida N.
    • Journal Title

      Mechanisms of Development

      Volume: 135 Pages: 31-42

    • DOI

      10.1016/j.mod.2014.10.001

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of FGF2-dependent pluripotent stem cells showing naive state characteristics from murine preimplantation inner cell mass.2014

    • Author(s)
      Ozawa, M., Kawakami, E., Sakamoto, R., Shibasaki, T., Goto, A. and Yoshida, N.
    • Journal Title

      Stem Cell Research

      Volume: in press Issue: 1 Pages: 75-87

    • DOI

      10.1016/j.scr.2014.04.012

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] The histone demethylase FBXL10 regulates the proliferation of spermatogonia and ensures long-term sustainable spermatogenesis in mice2016

    • Author(s)
      Ozawa M, Fukuda T, Sakamoto R, Honda H, Yoshida N
    • Organizer
      49th Annual Meeting of the Society for the Study of Reproduction
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2016-07-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒストン脱メチル化酵素Kdm2aは精原細胞の自己複製と分化のバランスを調整する2015

    • Author(s)
      小沢学 川上絵里 徳永暁憲 坂本怜子 吉田進昭
    • Organizer
      第38回 日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド 兵庫県神戸市
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Histone demethylases Fbxl11 regulates balance between self-renew and differentiation of spermatogonia in mice2015

    • Author(s)
      Ozawa M, Kawakami E, Tokunaga A, Sakamoto R, Yoshida N
    • Organizer
      48th Annual Meeting of the Society for the Study of Reproduction
    • Place of Presentation
      San Juan, Puerto Rico, USA
    • Year and Date
      2015-06-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒストン脱メチル化酵素Fbxl10はマウス精原細胞の加齢を抑制することで持続的な精子形成を調整する2014

    • Author(s)
      小沢学,福田剛,坂本怜子,吉田進昭
    • Organizer
      高遠分子細胞生物学シンポジウム
    • Place of Presentation
      長野県伊那市
    • Year and Date
      2014-08-28 – 2014-08-29
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒストン脱メチル化酵素Kdm2aによる精子形成の制御機序2013

    • Author(s)
      小沢学 川上絵里 徳永暁憲 坂本怜子 吉田進昭
    • Organizer
      日本繁殖生物学会
    • Place of Presentation
      東京農工大学
    • Related Report
      2013 Research-status Report
  • [Presentation] 小沢学、福田剛、坂本怜子、吉田進昭2013

    • Author(s)
      Fbxl10は精原細胞の加齢を抑制することで持続的な精子形成を保証する
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒストンのエピジェネティック修飾に よる持続的精子形成の維持機序の探索2013

    • Author(s)
      小沢学
    • Organizer
      日本分子生物学会 ランチョンセミナー
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Histone demethylases Fbxl10 and its homolog Fbxl11 regulate male germ cell development and sustainable spermatogenesis by different methods in mice2013

    • Author(s)
      Ozawa M, Kawakami E, Fukuda T, Sakamoto R, Yoshida N
    • Organizer
      Society for the Study of Reproduction
    • Place of Presentation
      Montreal, Canada
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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