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Role of CDK inhibitors in self-renewal regulation of spermatogonial stem cell

Research Project

Project/Area Number 26293064
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKyoto University

Principal Investigator

Shinohara Mito  京都大学, 医学(系)研究科(研究院), 助教 (10372591)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords幹細胞 / 細胞周期 / 生殖 / 自己複製
Outline of Final Research Achievements

In this project, we investigated the involvement of p57 gene, one of the Cyclin-dependent kinase inhibitors (CDKIs), in the regulation of self-renewal and maintenance of spermatogonial stem cells (SSCs). The results showed that the expression of p57 gene was upregulated in SSCs by FGF2 and GDNF, the self-renewal factors of SSCs. Using cultured SSC cell lines, which were derived from conditional knockout mice of p57 gene, we identified that self-renewal activity of SSCs was reduced in vitro by p57 gene deficiency. To elucidate the signaling pathway, which mediates the effect of p57 gene, we screened for molecules by microarray analysis, whose expression levels were affected by p57 gene deficiency. Involvements of some of these molecules were confirmed by overexpression or knockdown in cultured SSC cell line.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (26 results)

All 2017 2016 2015 2014

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 10 results,  Open Access: 9 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal.2016

    • Author(s)
      Kanatsu-Shinohara M., Tanaka T., Ogonuki N., Ogura A., Morimoto H., Cheng PF., Eisenman RN., Trumpp A., Shinohara T.
    • Journal Title

      Genes Dev.

      Volume: 30(23) Issue: 23 Pages: 2637-2648

    • DOI

      10.1101/gad.287045.116

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The luteinizing hormone-testosterone pathway regulates mouse spermatogonial stem cell self-renewal by suppressing WNT5A expression in Sertoli cells.2016

    • Author(s)
      Tanaka T., Kanatsu-Shinohara M., Lei Z., Rao CV., Shinohara T.
    • Journal Title

      Stem Cell Reports

      Volume: 7(2) Issue: 2 Pages: 279-291

    • DOI

      10.1016/j.stemcr.2016.07.005

    • NAID

      120005825924

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Nonrandom germline transmission of mouse spermatogonial stem cells.2016

    • Author(s)
      Kanatsu-Shinohara M., Naoki H., Shinohara T.
    • Journal Title

      Dev Cell

      Volume: 38 (3) Issue: 3 Pages: 248-261

    • DOI

      10.1016/j.devcel.2016.07.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Fertility of male germline stem cells following spermatogonial transplantation in infertile mouse models.2016

    • Author(s)
      Kanatsu-Shinohara M., Morimoto H., Shinohara T.
    • Journal Title

      Biol Reprod.

      Volume: 94(5) Issue: 5 Pages: 112-112

    • DOI

      10.1095/biolreprod.115.137869

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enrichment of Mouse Spermatogonial Stem Cells by the Stem Cell Dye CDy1.2015

    • Author(s)
      Kanatsu-Shinohara M, Morimoto H, Shinohara T.
    • Journal Title

      Biology of reproduction

      Volume: 94 (1) 13 Issue: 1 Pages: 1-10

    • DOI

      10.1095/biolreprod.115.135707

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pluripotent cell derivation from male germline cells by suppression of <i>Dmrt1</i> and <i>Trp53</i>2015

    • Author(s)
      Tanaka, T., Kanatsu-Shinohara, M., Hirose, M., Ogura, A., Shinohara, T.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 61 Issue: 5 Pages: 473-484

    • DOI

      10.1262/jrd.2015-059

    • NAID

      130005104118

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The CDKN1B-RB1-E2F1 pathway protects mouse spermatogonial stem cells from genomic damage2015

    • Author(s)
      Tanaka, T., Kanatsu-Shinohara, M., Shinohara, T.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 61 Issue: 4 Pages: 305-316

    • DOI

      10.1262/jrd.2015-027

    • NAID

      130005094647

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ROS-Generating Oxidase Nox3 Regulates the Self-Renewal of Mouse Spermatogonial Stem Cells2015

    • Author(s)
      Morimoto H, Kanatsu-Shinohara M, Shinohara T.
    • Journal Title

      Biology of reproduction

      Volume: 92 (6) 147 Issue: 6 Pages: 1-10

    • DOI

      10.1095/biolreprod.114.127647

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Functional differences between GDNF-dependent and FGF2-dependent mouse spermatogonial stem cell self-renewal.2015

    • Author(s)
      Takashima S, Kanatsu-Shinohara M, Tanaka T, Morimoto H, Inoue K, Ogonuki N, Jijiwa M, Takahashi M, Ogura A, Shinohara T.
    • Journal Title

      Stem Cell Reports.

      Volume: 4 Issue: 3 Pages: 489-502

    • DOI

      10.1016/j.stemcr.2015.01.010

    • NAID

      120005540400

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Trp53-Trp53inp1-Tnfrsf10b Pathway Regulates the Radiation Response of Mouse Spermatogonial Stem Cells.2014

    • Author(s)
      Kei Ishii, Masamichi Ishiai, Hiroko Morimoto, Mito Kanatsu-Shinohara, Ohtsura Niwa, Minoru Takata, and Takashi Shinohara.
    • Journal Title

      Stem Cell Reports.

      Volume: 3 Issue: 4 Pages: 676-89

    • DOI

      10.1016/j.stemcr.2014.08.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Improved serum- and feeder-free culture of mouse germline stem cells.2014

    • Author(s)
      Kanatsu-Shinohara M, Ogonuki N, Matoba S, Morimoto H, Ogura A, Shinohara T.
    • Journal Title

      Biol Reprod.

      Volume: 91 Issue: 4 Pages: 88-88

    • DOI

      10.1095/biolreprod.114.122317

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates spermatogonial stem cell self-renewal2014

    • Author(s)
      Kanatsu-Shinohara, M., Onoyama, I., Nakayama, K. I., Shinohara, T.
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A.

      Volume: 111 Issue: 24 Pages: 8826-8831

    • DOI

      10.1073/pnas.1401837111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2017

    • Author(s)
      篠原美都
    • Organizer
      生命動態システム科学四拠点 合同シンポジウム
    • Place of Presentation
      理化学研究所 生命システム研究センター
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2017

    • Author(s)
      篠原美都
    • Organizer
      JST 戦略的創造研究推進事業(さきがけ)第10回「細胞機能の構成的な理解と制御」領域会議
    • Place of Presentation
      淡路夢舞台国際会議場
    • Year and Date
      2017-02-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2016

    • Author(s)
      篠原美都
    • Organizer
      JST 戦略的創造研究推進事業(さきがけ)H25年度採択(第三期)研究成果報告会 「細胞機能の構成的な理解と制御」
    • Place of Presentation
      東京大学・理学部化学講堂
    • Year and Date
      2016-11-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] 長期培養系を用いた精子幹細胞の老化メカニズムの解明2016

    • Author(s)
      篠原美都
    • Organizer
      新学術領域「幹細胞老化と疾患」第三回領域会議
    • Place of Presentation
      東京大学 伊藤国際学術研究センター
    • Year and Date
      2016-06-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2016

    • Author(s)
      篠原美都
    • Organizer
      JST 戦略的創造研究推進事業(さきがけ)第9回「細胞機能の構成的な理解と制御」領域会議
    • Place of Presentation
      福岡県福岡市 ホテル ザ・ルイガンズ
    • Year and Date
      2016-06-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Nonrandom germline transmission of mouse spermatogonial stem cells2016

    • Author(s)
      Takashi Shinohara, Honda Naoki, and Mito Kanatsu-Shinohara
    • Organizer
      文部科学省 科学研究費補助金 新学術領域研究 「生殖細胞のエピゲノムダイナミクスとその制御」による国際シンポジウム Epigenome Dynamics and Regulation in Germ cells
    • Place of Presentation
      Clock Tower Centennial Hall, Kyoto University
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enrichment of mouse spermatogonial stem cells by a stem cell dye CDy12016

    • Author(s)
      Mito Kanatsu-Shinohara, Hiroko Morimoto, and Takashi Shinohara
    • Organizer
      科学研究費補助金 新学術領域研究 「生殖細胞のエピゲノムダイナミクスとその制御」による国際シンポジウム Epigenome Dynamics and Regulation in Germ cells
    • Place of Presentation
      Clock Tower Centennial Hall, Kyoto University
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2015

    • Author(s)
      篠原美都
    • Organizer
      JST 戦略的創造研究推進事業(さきがけ)第8回「細胞機能の構成的な理解と制御」領域会議
    • Place of Presentation
      東京白金台・八芳園
    • Year and Date
      2015-11-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2015

    • Author(s)
      篠原美都
    • Organizer
      JST 戦略的創造研究推進事業(さきがけ)H24年度採択(第二期)研究成果報告会 「細胞機能の構成的な理解と制御」
    • Place of Presentation
      東京大学・伊藤謝恩ホール
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2015

    • Author(s)
      篠原美都
    • Organizer
      JST 戦略的創造研究推進事業(さきがけ)第7回「細胞機能の構成的な理解と制御」領域会議
    • Place of Presentation
      IBM天城ホームステッド
    • Year and Date
      2015-07-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 長期培養系を用いた精子幹細胞の老化メカニズムの解明2015

    • Author(s)
      篠原美都
    • Organizer
      新学術領域「幹細胞老化と疾患」第二回領域会議
    • Place of Presentation
      新潟グランドホテル
    • Year and Date
      2015-06-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2015

    • Author(s)
      篠原 美都
    • Organizer
      JST 戦略的創造研究推進事業(さきがけ)第6回「細胞機能の構成的な理解と制御」領域会議
    • Place of Presentation
      北海道虻田郡留寿都村 ルスツリゾートホテル
    • Year and Date
      2015-02-02 – 2015-02-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2015

    • Author(s)
      篠原 美都
    • Organizer
      JST 戦略的創造研究推進事業 さきがけ細胞構成領域3期生第2回自主勉強会『生物学の向こうへ』
    • Place of Presentation
      日本文理大学湯布院研修所
    • Year and Date
      2015-01-10 – 2015-01-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 精子幹細胞の寿命と精子形成への寄与の動態解明2014

    • Author(s)
      篠原 美都
    • Organizer
      JST 戦略的創造研究推進事業(さきがけ)第5回「細胞機能の構成的な理解と制御」領域会議
    • Place of Presentation
      IBM天城ホームステッド
    • Year and Date
      2014-05-11 – 2014-05-13
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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