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Analysis of epigenome stability and germ cell tumor formation

Planned Research

Project AreaAnalyses and regulation of germline epigenome
Project/Area Number 25112003
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

Shinohara Takashi  京都大学, 医学研究科, 教授 (30322770)

Project Period (FY) 2013-06-28 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥201,500,000 (Direct Cost: ¥155,000,000、Indirect Cost: ¥46,500,000)
Fiscal Year 2017: ¥41,990,000 (Direct Cost: ¥32,300,000、Indirect Cost: ¥9,690,000)
Fiscal Year 2016: ¥41,990,000 (Direct Cost: ¥32,300,000、Indirect Cost: ¥9,690,000)
Fiscal Year 2015: ¥41,990,000 (Direct Cost: ¥32,300,000、Indirect Cost: ¥9,690,000)
Fiscal Year 2014: ¥41,990,000 (Direct Cost: ¥32,300,000、Indirect Cost: ¥9,690,000)
Fiscal Year 2013: ¥33,540,000 (Direct Cost: ¥25,800,000、Indirect Cost: ¥7,740,000)
Keywords精子形成 / がん / 解糖系 / 精子幹細胞 / 生殖細胞
Outline of Final Research Achievements

In 2004, we discovered that cultured spermatogonial stem cells, designated as germline stem (GS) cells, can spontaneously dedifferentiate into embryonic stem (ES) cell-like multipotent GS cells. However, the frequency of conversion was very low and the mechanism underlying this dedifferentiation remained unknown. In this research, we found that DNA demethylation in GS cells induces downregulation of Dmrt1, which is one of the germ cell tumor genes. This Dmrt1 downregulation leads to induce Sox2 gene, which is one of the essential genes involved in the maintenance of ES cells. Our results suggest that epigenetic abnormalities in GS cells are responsible for the acquisition of pluripotency in GS cells.

Report

(6 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (31 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (3 results) Journal Article (21 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 21 results,  Open Access: 11 results,  Acknowledgement Compliant: 13 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Texas at San Antonio/University of Pittsburgh(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Florida/Fred Hutchinson Cancer Research Center/Pittsuburgh Univeristy(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] McGill University(カナダ)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Transfer of a mouse artificial chromosome into spermatogonial stem cells genetates transchromosomic mice,2017

    • Author(s)
      Shinohara T, Kazuki K, Ogonuki N, Morimoto H, Matoba S, Hiramatsu K, Honma K, Suzuki T, Hara T, Ogura A, Oshimura M, Kanatsu-Shinohara M, Kazuki Y.
    • Journal Title

      Stem Cell Reports.

      Volume: 9(4) Issue: 4 Pages: 1180-1191

    • DOI

      10.1016/j.stemcr.2017.08.012

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nonrandom contribution of left and right testes to germline transmission from mouse spermatogonial stem cells2017

    • Author(s)
      Mito Kanatsu-Shinohara, Honda Naoki, Takashi Shinohara
    • Journal Title

      Biology of Reproduction

      Volume: 97(6) Issue: 6 Pages: 902-910

    • DOI

      10.1093/biolre/iox141

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adeno-associated virus-mediated delivery of genes into mouse spermatogonial stem cells.2017

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

      Biol. Reprod.

      Volume: 96 Pages: 221-231

    • DOI

      10.1095/biolreprod.116.143495

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [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
      2015 Annual Research 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
  • [Journal Article] Cell-cycle-dependent colonization of mouse spermatogonial stem cells after transplantation into seminiferous tubules.2014

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

      J Reprod Dev

      Volume: 60 Pages: 37-46

    • NAID

      130003381858

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ROS are required for mouse spermatogonial stem cell self-renewal.2013

    • Author(s)
      Morimoto H, Iwata K, Ogonuki N, Inoue K, Atsuo O, Kanatsu-Shinohara M, Morimoto T, Yabe-Nishimura C, Shinohara T.
    • Journal Title

      Cell Stem Cell.

      Volume: 12 Issue: 6 Pages: 774-86

    • DOI

      10.1016/j.stem.2013.04.001

    • NAID

      120005285490

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of pluripotency in male germline stem cells by Dmrt1.2013

    • Author(s)
      Takashima S, Hirose M, Ogonuki N, Ebisuya M, Inoue K, Kanatsu-Shinohara M, Tanaka T, Nishida E, Ogura A, Shinohara T.
    • Journal Title

      Genes Dev.

      Volume: 27 Issue: 18 Pages: 1949-58

    • DOI

      10.1101/gad.220194.113

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Symposium in honor of Ralph L. Brinster celebrating 50 years of scientific breakthroughs.2013

    • Author(s)
      Behringer RR, Shinohara T.
    • Journal Title

      Int J Dev Biol

      Volume: 57 Issue: 5 Pages: 333-339

    • DOI

      10.1387/ijdb.120248rb

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enrichment of mouse spermatogonial stem cells based on aldehyde dehydrogenase activity.2013

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

      Biol Reprod.

      Volume: 89 Issue: 6 Pages: 140-140

    • DOI

      10.1095/biolreprod.113.114629

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spermatogonial stem cell self-renewal and development.2013

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

      Annu Rev Cell Dev Biol.

      Volume: 29 Issue: 1 Pages: 163-87

    • DOI

      10.1146/annurev-cellbio-101512-122353

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Fertility and spermatogonial stem cells2017

    • Author(s)
      Takashi Shinohara
    • Organizer
      American Society of Andrology 2017 42nd Annual Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Myc-mediated glycolysis enhances spermatogonial stem cell self-renewal.2017

    • Author(s)
      篠原隆司
    • Organizer
      第15回幹細胞シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 精子幹細胞の遺伝情報パターン2017

    • Author(s)
      篠原隆司
    • Organizer
      放射線影響学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Non-random germline transmission of mouse spermatogonial stem cells2016

    • Author(s)
      Takashi Shinohara
    • Organizer
      international symposium on epigenome dynamics and regulation in germ cells
    • Place of Presentation
      京都大学
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of spermatogonial stem cell self-renewal.2014

    • Author(s)
      Takashi Shinohara
    • Organizer
      Society for Reproduction and Fertility annual conference 2014
    • Place of Presentation
      英国(エジンバラ)
    • Year and Date
      2014-09-02
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 活性酸素の精子形成における役割2013

    • Author(s)
      篠原隆司
    • Organizer
      生殖エピゲノム班班会議
    • Place of Presentation
      大阪大学微生物病研究所
    • Year and Date
      2013-11-15 – 2013-11-16
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 雄性生殖細胞またはセルトリ細胞にポリヌクレオチドを導入する方法2017

    • Inventor(s)
      篠原隆司、渡邉哲史
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2013-07-10   Modified: 2019-03-29  

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