Transcription factors regulating normal and pathological platelet differentiation

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390022
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Osaka 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
• Keywords: 血小板 / 遺伝子発現制御 / 分化 / RUNX1

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

Research Products

• [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
• [Journal Article] Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation (2010)
  • Author(s): N. Yamano, T. Kimura, S. Watanabe-Kushima, T. Shinohara, T. Nakano
  • Journal Title: Biochem. Biophys. Res. Commun Vol.392 Pages: 311-316
  • 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
• [Journal Article] Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1 (2009)
  • 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
  • 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 mice (2009)
  • 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
  • Peer Reviewed
• [Journal Article] Differential roles for ETS, CREB and EGR binding sites in mediating VEGF receptor 1 expression in vivo (2009)
  • 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
  • Peer Reviewed
• [Journal Article] Associations between PIWI proteins and TDRD1/MTR-1 are critical for integrated subcellular localization in murine male germ cell (2009)
  • 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
  • Peer Reviewed
• [Journal Article] Increase of hematopoietic progenitor and suppression of endothelial gene expression by Runx1 expression during in vitro ES differentiation (2009)
  • Author(s): E. Sakai, K. Kitajima, A. Sato, T. Nakano
  • Journal Title: Exp. Hematol Vol.37 Pages: 334-345
  • Peer Reviewed
• [Journal Article] A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Differential context-dependent effects of friend of GATA-1 (FOG-1) on mast-cell development and differentiation (2008)
  • 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
  • Peer Reviewed
• [Journal Article] A Three-Kilobase Fragment of the Human Robo4 Promoter Directs Cell Type-Specific Expression in Endothelium (2007)
  • 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
  • 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
• [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
• [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
• [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
• [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
• [Remarks]
  • URL: http://www.phs.osaka-u.ac.jp/homepage/b018/