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Sex specification of germline cells by epigenetic regulation in mice

Research Project

Project/Area Number 15H02472
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Animal production science
Research InstitutionTokyo University of Agriculture

Principal Investigator

Kono Tomohiro  東京農業大学, 生命科学部, 教授 (80153485)

Co-Investigator(Kenkyū-buntansha) 小林 久人  東京農業大学, その他部局等, 准教授 (70632727)
外丸 祐介  広島大学, 自然科学研究支援開発センター, 教授 (90309352)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥42,380,000 (Direct Cost: ¥32,600,000、Indirect Cost: ¥9,780,000)
Fiscal Year 2017: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
Fiscal Year 2016: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2015: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Keywordsエピジェネティクス / 始原生殖細胞 / 性分化 / トランスクリプトーム / ヒストン修飾 / ChIP-seq / 性転換 / CRISPR/Cas9 / 生殖細胞形成異常 / Sry欠損 / 卵母細胞 / エピゲノム / 生殖系列細胞 / 次世代シークエンサー / Sry欠損性転換マウス / トランスクリプトーム解析 / 3Dイメージング / 発生・分化 / ゲノム編集 / 性転換マウス
Outline of Final Research Achievements

We conducted studies on mechanisms underlying sex differentiation of mouse primordial germ cells (PGCs). By transcriptome analysis, we identified gene expression profiles specific for male and female PGCs, respectively; which could lead sex differences at early stage of PGCs. We successfully obtained global information of comprehensive histone modifications of PGCs by ChIP-seq analysis. Interestingly the data demonstrated sex specific difference of histone modifications, which would regulate sex specific gene expression of PGCs. Furthermore, transgenic mice lacking Sry, sex-determining region Y, were produced by genome editing procedure and we showed molecular mechanism underlying depletion and dysfunction of XY oocytes. This project provides further insight into epigenetic regulation for differentiation of female and male germ cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (16 results)

All 2017 2016 2015

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 3 results) Funded Workshop (1 results)

  • [Journal Article] Repetitive DNA methylome analysis by small-scale and single-cell shotgun bisulfite sequencing.2016

    • Author(s)
      Kobayashi H, Koike T, Sakashita A, Tanaka K, Kumamoto S, Kono T
    • Journal Title

      Genes Cells

      Volume: 21 Issue: 11 Pages: 1209-1222

    • DOI

      10.1111/gtc.12440

    • NAID

      130007024787

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DNA Methylation Errors in Cloned Mouse Sperm by Germ Line Barrier Evasion2016

    • Author(s)
      Koike T, Wakai T, Jincho Y, Sakashita A, Kobayashi H, Mizutani E, Wakayama S, Miura F, Ito T, Kono T
    • Journal Title

      Biol Reprod

      Volume: 94 Issue: 6 Pages: 1-7

    • DOI

      10.1095/biolreprod.116.138677

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell proliferation potency is independent of FGF4 signaling in trophoblast stem cells derived from androgenetic embryos2016

    • Author(s)
      Ogawa H, Takyu R, Morimoto H, Toei S, Sakon H, Goto S, Moriya S, Kono T.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 62 Issue: 1 Pages: 51-58

    • DOI

      10.1262/jrd.2015-097

    • NAID

      130005126319

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Complete in vitro generation of fertile oocytes from mouse primordial germ cells2016

    • Author(s)
      Morohaku K, Tanimoto R, Sasaki K, Kawahara-Miki R, Kono T, Hayashi K, Hirao Y, Obata Y.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 113 Issue: 32 Pages: 9021-9026

    • DOI

      10.1073/pnas.1603817113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sex Specification and Heterogeneity of Primordial Germ Cells in Mice.2015

    • Author(s)
      Sakashita, A., Kawabata, Y., Jincho, Y., Tajima, S., Kumamoto, S., Kobayashi, H., Matsui, Y. and Kono, T.
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 12 Pages: 1-21

    • DOI

      10.1371/journal.pone.0144836

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Sry欠損XY性転換雌マウスの卵母細胞成熟能および繁殖能の解析2017

    • Author(s)
      西村千秋, 坂下陽彦, 河野友宏
    • Organizer
      第58回 日本卵子学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Single-cell transcriptome analysis in XY oocytes of SRY-mutated, sex-reversed mice2017

    • Author(s)
      Akihiko SAKASHITA, Chiaki NISHIMURA, Tomohiro Kono
    • Organizer
      World Congress of Reproductive Biology 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] XY oocytes of sex-reversed mice with Sry mutation deviate from the differentiation process at initial stages2016

    • Author(s)
      Akihiko SAKASHITA, Chiaki NISHIMURA, Hisato KOBAYASHI, Yusuke SOTOMARU, Tomohiro KONO
    • Organizer
      分子生物学会
    • Place of Presentation
      神奈川県、横浜、パシフィコ横浜
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脱メチル化完了後のマウス始原生殖細胞におけるヒストン修飾の役割2016

    • Author(s)
      川畑順子、神尾明日香、神長祐子、高島友弥、坂下陽彦、小林久人、河野友宏
    • Organizer
      分子生物学会
    • Place of Presentation
      神奈川県、横浜、パシフィコ横浜
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] マウス生殖細胞および初期発生胚のDNAメチローム解析2016

    • Author(s)
      小林 久人、小池 佐、坂下 陽彦、都能 遼、隈本 宗一郎、若井 拓也、佐野 賢、河野 友宏
    • Organizer
      分子生物学会
    • Place of Presentation
      神奈川県、横浜、パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA methylome analysis in mouse germ cells and early embryos2016

    • Author(s)
      Tomohiro Kono, Hisato Kobayashi, Tasuku Koike, Akihiko Sakashita, Haruka Tsuno, Soichiro Kumamoto, Takuya Wakai, Satoshi Sano
    • Organizer
      ESHRE
    • Place of Presentation
      Finland, Helsinki, Mussukeskus
    • Year and Date
      2016-07-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ホールマウント免疫染色法を用いたPGCsの計数とアポトーシスの検出2016

    • Author(s)
      田島紫雲、井関陽介、小川英彦、尾畑やよい、河野友宏
    • Organizer
      日本卵子学会
    • Place of Presentation
      新潟県、新潟市、ときメッセ
    • Year and Date
      2016-05-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Regulation of Gender Specific Gene Expression in mouse Primordial Germ Cells2015

    • Author(s)
      Akihiko Sakashita, Yukiko Kawabata, Yuko Jincho, Shiun Tajima, Souichiro Kumamoto, Hisato Kobayashi, Yasuhisa Matsui, Tomohiro Kono
    • Organizer
      Epigenetics 2015
    • Place of Presentation
      Tasmania, Australia
    • Year and Date
      2015-11-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス始原生殖細胞の遺伝子発現を制御するエピゲノム修飾2015

    • Author(s)
      神長祐子, 川畑順子, 坂下陽彦, 小林久人、河野友宏
    • Organizer
      日本繁殖生物学会
    • Place of Presentation
      宮崎大学
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウス始原生殖細胞におけるDNAメチル化非依存的な性特異的遺伝子発現機構2015

    • Author(s)
      坂下 陽彦, 田島 紫雲, 川畑 順子, 神長 裕子, 小林 久人, 河野 友宏
    • Organizer
      日本卵子学会
    • Place of Presentation
      宇都宮
    • Year and Date
      2015-05-30
    • Related Report
      2015 Annual Research Report
  • [Funded Workshop] World Congress of Reproductive Biology 20172017

    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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