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Identification of regulatory molecules governing self-renewal versus differentiation of spermatogonial stem cells

Research Project

Project/Area Number 23380168
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied animal science
Research InstitutionKitasato University

Principal Investigator

Kubota Hiroshi  北里大学, 獣医学部, 教授 (80263094)

Co-Investigator(Kenkyū-buntansha) 垣内 一恵  北里大学, 獣医学部, 助教 (90509184)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2011: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Keywords生殖幹細胞 / 精原幹細胞 / 精子形成 / 自己複製 / 幹細胞 / 分化・発生 / 生殖 / バイオテクノロジー
Outline of Final Research Achievements

Comparative gene expression analysis between differentiation-deficient spermatogonial stem cells (SSCs) and wild-type SSCs indicated that the KIT expression involves in maintaining an undifferentiated state of SSCs. Factor X was identified as one of the genes that were down-regulated in differentiation-deficient SSCs. Factor X expression was restricted in undifferentiated spermatogonia including SSCs in murine testes. Down regulation of Factor X in cultured SSCs induced differentiation. On the other hand, when Factor X was over-expressed in cultured SSCs, their self-renewing proliferation was dramatically impaired. These results suggest that Factor X, which was identified in this study, is a regulatory molecule governing self-renewal and differentiation of murine SSCs.

Academic Significance and Societal Importance of the Research Achievements

本研究課題において、精原幹細胞の自己複製と分化を制御する新たな因子として因子Xが同定された。これまで発現量の低下により分化を誘導する因子は複数同定されているが、過剰発現により自己複製増殖を阻害する因子は同定されていない。因子Xの過剰発現による自己複製増殖の阻害は休止状態への移行である可能性がある。組織内で最も未熟な幹細胞は休止状態にあるため、因子Xの発現がそうした休止状態への移行に関与している可能性について検証することは重要である。今後の課題は、因子Xがいかに精原幹細胞の自己複製増殖と分化誘導を制御しているかを明らかにすることである。

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • Research Products

    (12 results)

All 2014 2013 2012 2011

All Journal Article (3 results) (of which Peer Reviewed: 1 results) Presentation (9 results)

  • [Journal Article] Cell-Surface DEAD-Box Polypeptide 4-Immunoreactive Cells and Gonocytes Are Two Distinct Populations in Postnatal Porcine Testes2014

    • Author(s)
      Kazue Kakiuchi, Ayaka Tsuda, Yuki Goto, Takanori Shimada, Kazumi Taniguchi, Kiyohiko Takagishi, Hiroshi Kubota
    • Journal Title

      Biology of Reproduction

      Volume: 90 Pages: 82-82

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cell-Surface DEAD-Box Polypeptide 4-Immunoreactive Cells and Gonocytes Are Two Distinct Populations in Postnatal Porcine Testes2014

    • Author(s)
      Kakiuchi K, Tsuda A, Goto Y, Shimada T, Taniguchi K, Takagishi K, Kubota H
    • Journal Title

      Biology of Reproduction

      Volume: 90 Issue: 4 Pages: 1-11

    • DOI

      10.1095/biolreprod.113.114405

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glial cell line-derived neurotrophic factor and endothelial cells promote self-renewal of rabbit germ cells with spermatogonial stem cell properties2011

    • Author(s)
      Hiroshi Kubota, Xin Wu, Shaun M Goodyear, Mary R Avarbock, Ralph L Brinster
    • Journal Title

      FASEB Journal

      Volume: 25 Pages: 2604-2614

    • Related Report
      2013 Final Research Report
  • [Presentation] Proteomic profiling of nuclear proteins in mouse spermatogonial stem cells undergoing differentiation2013

    • Author(s)
      Kazue Kakiuchi, Kiyohiko Takagishi, Hiroshi Kubota
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Year and Date
      2013-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Proteomic profiling of nuclear proteins in mouse spermatogonial stem cells undergoing differentiation2013

    • Author(s)
      Kakiuchi K, Takagishi K, Kubota H.
    • Organizer
      第36回 日本分子生物学会
    • Place of Presentation
      兵庫県 神戸ポートアイランド
    • Year and Date
      2013-12-03
    • Related Report
      2013 Annual Research Report
  • [Presentation] Comparative nuclear proteomic analysis of stem spermatogonia and differentiating spermatogonia induced by retinoic acid2013

    • Author(s)
      Kazue Kakiuchi, Kiyohiko Takagishi, Hiroshi Kubota
    • Organizer
      12th Human Proteome Organization World Congress (HUPO2013)
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2013-09-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Comparative nuclear proteomic analysis of stem spermatogonia and differentiating spermatogonia induced by retinoic acid2013

    • Author(s)
      Kakiuchi K, Takagishi K, Kubota H.
    • Organizer
      12th Human Proteome Organisation World Congress (HUPO 2013)
    • Place of Presentation
      神奈川県 パシフィコ横浜
    • Year and Date
      2013-09-14
    • Related Report
      2013 Annual Research Report
  • [Presentation] Comparative nuclear proteomic analysis of spermatogonial stem cells and differentiating spermatogonia induced by retinoic acid2013

    • Author(s)
      垣内一恵
    • Organizer
      12th Human Proteome Organisation World Congress (HUPO 2013)
    • Place of Presentation
      神奈川県 パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] マウス精原幹細胞における核タンパク質のプロテオーム解析2012

    • Author(s)
      垣内 一恵, 高岸 聖彦, 久保田 浩司
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      マリンメッセ福岡(福岡)
    • Year and Date
      2012-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] 成熟培地への糖基質の添加がブタ卵丘細胞のヒアルロン酸合成に及ぼす影響2012

    • Author(s)
      高岸 聖彦, 小林 君任, 垣内 一恵, 久保田 浩司
    • Organizer
      第30回日本受精着床学会総会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2012-08-30
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス精原幹細胞における核タンパク質のプロテオーム解析2012

    • Author(s)
      垣内一恵
    • Organizer
      第35回 日本分子生物学会
    • Place of Presentation
      福岡県 マリンメッセ福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 非齧歯類哺乳動物の精原幹細胞培養系2011

    • Author(s)
      久保田 浩司
    • Organizer
      第104日本繁殖生物学会
    • Place of Presentation
      いわて県民情報交流センター・アイーナ (岩手)
    • Year and Date
      2011-09-17
    • Related Report
      2013 Final Research Report

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Published: 2011-04-06   Modified: 2025-01-30  

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