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Transcription factors regulating normal and pathological platelet differentiation

Research Project

Project/Area Number 19390022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionOsaka University

Principal Investigator

DOI Takefumi  Osaka University, 大学院・薬学研究科, 教授 (00211409)

Co-Investigator(Kenkyū-buntansha) OKADA Yoshiaki  大阪大学, 大学院・薬学研究科, 助教 (50444500)
NAKANO Toru  大阪大学, 大学院・生命機能研究科, 教授 (00172370)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2009: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2008: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2007: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Keywords血小板 / 遺伝子発現制御 / 分化 / RUNX1 / 転写因子 / 巨核球 / ES細胞 / Hprt ターゲティング法 / OP9
Research Abstract

To understand the molecular mechanism for platelet production from hematopoietic stem cells, we focused on the Runx1 gene, which is closely related to familial platelet disorder (FPD). In the current study, RUNX1 is shown to bind to the promoter sequence of the PF4 gene, which is expressed only in platelet lineage, and cooperatively activate the promoter with ETS family proteins, ETS-1 and FLI-1. On the other hand, RUNX1 mutants found in the FPD patients could not activate the promoter. To understand the functional difference between wild type and mutant RUNX1 in physiological platelet differentiation, a novel ES cell differentiation system was established, in which exogenous genes can be overexpressed only in platelet lineage

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (30 results)

All 2010 2009 2008 2007 Other

All Journal Article (21 results) (of which Peer Reviewed: 17 results) Presentation (7 results) Remarks (2 results)

  • [Journal Article] in vitroとin vivoで異なるレポータージーンアッセイの結果2010

    • Author(s)
      岡田欣晃、土井健史
    • Journal Title

      生産と技術 62巻

      Pages: 51-56

    • NAID

      40017231022

    • Related Report
      2009 Final Research Report
  • [Journal Article] Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation2010

    • Author(s)
      N. Yamano, T. Kimura, S. Watanabe-Kushima, T. Shinohara, T. Nakano
    • Journal Title

      Biochem. Biophys. Res. Commun Vol.392

      Pages: 311-316

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] in vitroとin vivoで異なるレポータージーンアッセイの結果2010

    • Author(s)
      岡田欣晃
    • Journal Title

      生産と技術 62

      Pages: 51-56

    • NAID

      40017231022

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation.2010

    • Author(s)
      Noriko Yamano
    • Journal Title

      Biochemical and Biophysical Research Communications 392

      Pages: 311-316

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血管内皮細胞の遺伝子発現制御研究からみたin vivoプロモーター解析の重要性2009

    • Author(s)
      岡田欣晃, 土井健史
    • Journal Title

      生化学 80巻

      Pages: 117-121

    • NAID

      10024915912

    • Related Report
      2009 Final Research Report
  • [Journal Article] Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR12009

    • Author(s)
      K.H. Baek, A. Zaslavsky, R.C. Lynch, C. Britt, Y. Okada, R.J. Siarey, M.W. Lensch, I.H. Park, S.S. Yoon, T. Minami, J.R. Korenberg, J. Folkman, G.Q. Daley, W.C. Aird, Z. Galdzicki, S. Ryeom
    • Journal Title

      Nature Vol.459

      Pages: 1126-1130

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgenic mice2009

    • Author(s)
      J. Liu, Y. Kanki, Y. Okada, E. Jin, K. Yano, S.-C. Shih, T. Minami, W.C. Aird
    • Journal Title

      J. Thromb. Haemost Vol.284

      Pages: 22195-22205

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential roles for ETS, CREB and EGR binding sites in mediating VEGF receptor 1 expression in vivo2009

    • Author(s)
      E. Jin, J. Liu, J. Suehiro, L. Yaun, Y. Okada, V. Nikolova-Krstevski, K. Yano, L. Janes, D. Beeler, K. Spokes, E. Regan, S.C. Shih, P. Oettgen, T. Minami, W.C. Aird
    • Journal Title

      Blood Vol.114

      Pages: 5557-5566

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Associations between PIWI proteins and TDRD1/MTR-1 are critical for integrated subcellular localization in murine male germ cell2009

    • Author(s)
      K. Kojima, S. Kuramochi-Miyagawa, S. Chuma, T. Tanaka, N. Nakatsuji, T. Kimura, T. Nakano
    • Journal Title

      Genes. Cells Vol.14

      Pages: 1155-1165

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increase of hematopoietic progenitor and suppression of endothelial gene expression by Runx1 expression during in vitro ES differentiation2009

    • Author(s)
      E. Sakai, K. Kitajima, A. Sato, T. Nakano
    • Journal Title

      Exp. Hematol Vol.37

      Pages: 334-345

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] 血管内皮細胞の遺伝子発現制御研究からみたin vivoプロモーター解析の重要性2009

    • Author(s)
      岡田欣晃
    • Journal Title

      生化学 81

      Pages: 117-121

    • NAID

      10024915912

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR12009

    • Author(s)
      Kwan-Hyuck Baek
    • Journal Title

      Nature 459

      Pages: 1126-1130

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgenic mice2009

    • Author(s)
      Ju Liu
    • Journal Title

      Journal of thrombosis and haemostasis 284

      Pages: 22195-22205

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential roles for ETS, CREB and EGR binding sites in mediating VEGF receptor 1 expression in vivo2009

    • Author(s)
      Enjing Jin
    • Journal Title

      Blood 114

      Pages: 5557-5566

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Associations between PIWI proteins and TDRD1/MTR-1 are critical for integrated subcellular localization in murine male germ cell2009

    • Author(s)
      Kanako Kojima
    • Journal Title

      Genes to Cells 14

      Pages: 1155-1165

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increase of hematopoietic progenitor and suppression of endothelial gene expression by Runxl expression during in vitro ES differentiation2009

    • Author(s)
      Eiko Sakai
    • Journal Title

      Experimental Hematology 37

      Pages: 334-345

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo2008

    • Author(s)
      Y. Okada, E. Jin, V. Nikolova-Krstevski, K. Yano, J. Liu, D. Beeler, K. Spokes, M. Kitayama, N. Funahashi, T. Doi, L. Janes, T. Minami, P. Oettgen, W.C. Aird
    • Journal Title

      Blood Vol.112

      Pages: 2336-2339

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential context-dependent effects of friend of GATA-1 (FOG-1) on mast-cell development and differentiation2008

    • Author(s)
      D. Sugiyama, M. Tanaka, K. Kitajima, J. Zheng, H. Yen, T. Murotani, A. Yamatodani, T. Nakano
    • Journal Title

      Blood Vol.111

      Pages: 1924-1932

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo2008

    • Author(s)
      Yoshiaki Okada
    • Journal Title

      Blood 112

      Pages: 2336-2339

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Three-Kilobase Fragment of the Human Robo4 Promoter Directs Cell Type-Specific Expression in Endothelium2007

    • Author(s)
      Y. Okada, K. Yano, E. Jin, N. Funahashi, M. Kitayama, T. Doi, K. Spokes, D.L. Beeler, S-C. Shih, H. Okada, T.A. Danilov, E. Maynard, T. Minami, P. Oettgen, W.C. Aird
    • Journal Title

      Circulation Research Vol.100

      Pages: 1712-1722

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A three-kilobase fragment of the human Robo4 promoter directs cell type-specific expression in endothelium.2007

    • Author(s)
      Yoshiaki Okada
    • Journal Title

      Circulation Research 100(12)

      Pages: 1712-1722

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 家族性血小板減少症患者にみられる変異型RUNX1の機能解析2010

    • Author(s)
      渡邊美穂, 米倉正哲, 仲井友子, 登治謙, 志水美己子, 岡田欣晃, 土井健史
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山桃太郎アリーナ(岡山県)
    • Year and Date
      2010-03-30
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] 51 ETSサイトを介するPF4遺伝子の発現制御メカニズムの解明2009

    • Author(s)
      登治謙, 渡邊美穂, 米倉正哲, 志水美己子, 仲井友子, 岡田欣晃, 土井健史
    • Organizer
      第8回次世代を担う若手ファーマバイオフォーラム2009
    • Place of Presentation
      名古屋市立大学田辺通キャンパス(愛知県)
    • Year and Date
      2009-11-14
    • Related Report
      2009 Final Research Report
  • [Presentation] -51 ETSサイトを介するPF4遺伝子の発現制御メカニズムの解明2009

    • Author(s)
      登治謙
    • Organizer
      第8回次世代を担う若手ファーマバイオフォーラム2009
    • Place of Presentation
      名古屋市立大学田辺通キャンパス(愛知県)
    • Year and Date
      2009-11-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] 血小板第4因子遺伝子の発現制御における-51 ETSサイトの役割2009

    • Author(s)
      登治謙, 渡邊美穂, 米倉正哲, 岡田欣晃, 土井健史
    • Organizer
      第10回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      日本薬学会長井記念ホール(東京都)
    • Year and Date
      2009-06-19
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] -51 ETSサイトを介する血小板第4因子遺伝子の発現制御機構の解析2009

    • Author(s)
      登治謙, 渡邊美穂, 米倉正哲, 岡田欣晃, 土井健史
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2009-03-26
    • Related Report
      2009 Final Research Report
  • [Presentation] -51 ETSサイトを介する血小板第4因子遺伝子の発現制御機構の解析2009

    • Author(s)
      登 治謙
    • Organizer
      日本薬学会 第129年会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2009-03-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] 家族性血小板減少症(FPD)に見られるRUNX1変異体を血小板系列特異的に発現するES細胞株の樹立2008

    • Author(s)
      渡邊美穂, 北山美絵, 原敏郎, 米倉正哲, 登治謙, 山崎大典, William Aird, 北島健二, 仲野徹, 岡田欣晃, 土井健史
    • Organizer
      Biochemistry and Molecular Biology 2008
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2008-12-09
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.phs.osaka-u.ac.jp/homepage/b018/

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://www.phs.osaka-u.ac.jp/homepage/b018/

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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