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ES細胞を用いた新しい構成的発生生物学による分化におけるゲノム機能の網羅的解析

Research Project

Project/Area Number 18016013
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

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

Principal Investigator

山下 潤  Kyoto University, 再生医科学研究所, 准教授 (50335288)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2007: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsES細胞 / 血管 / 動静脈 / リンパ管 / 心臓 / 遺伝子プロファイル / 分化 / Flk1 / 動静脈分化 / リンパ管分化 / RNA干渉 / ヒトES細胞 / 分化メカニズム
Research Abstract

研究代表者等は、ES細胞(胚性幹細胞)を用いて血管および心臓の分化研究を行い、心血管分化過程を細胞レベルで経時的系統的に解析できる新しい分化システムを構築した(Nature, 2000; FASEB J, 2005)。本研究は、ヒトを含めた哺乳動物の発生及び細胞分化過程を構成的に再現し、その過程におけるゲノム機能のダイナミズムを細胞レベルで解析・提示できる新たな研究基盤の構築を目的とする。研究期間内においては、1)我々の新しいES細胞分化系を用いた心血管細胞分化過程における細胞レベルでの遺伝子プロファイルの作製、2)心血管分化における機能遺伝子の網羅的同定、3)同機能遺伝子群による構成的細胞分化の再現を行う。また、4)分化過程におけるゲノム構造変遷の可視化と5)同定遺伝子発現制御機構の解析により、個々の細胞分化におけるゲノム機能の経時的系統的解析を試みる。さらには6)ヒトES細胞を用いた構成的ヒト発生学の構築を試みる。本年度は、
1)動静脈分化における遺伝子プロファイルの作製:誘導した動静脈リンパ管内皮細胞を純化し遺伝子発現プロファイルを作製した。数々の動静脈リンパ管内皮特異的遺伝子を同定した。
2)心筋分化における遺伝子プロファイルの作製:心筋及び心筋前駆細胞特異的遺伝子群を同定。
3)心筋ペースメーカー細胞分化機構の解析(Yanagi, Stem Cells, 2007)。
4)ヒトES細胞血管分化誘導システムの構築(Sone, Arterioscler Thromb Vasc Biol, 2007)。
5)マウス人工多能性幹細胞(iPS細胞)を用いた心血管分化誘導システムの構築
6)ヒトiPS細胞を用いた心血管分化誘導。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (16 results)

All 2008 2007 2006 Other

All Journal Article (12 results) (of which Peer Reviewed: 7 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Augmentation of neovascularizaiton in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells.2008

    • Author(s)
      Yamahara K, Sone M, Itoh H, Yamashita JK, Nakao K., 他6名
    • Journal Title

      PLoS One (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic strain induces mouse embryonic Stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor (beta).2008

    • Author(s)
      Shimizu N, Yamamoto K, Obi S, Kumagaya S, Masumura T, Shimano Y, Naruse K, Yamashita JK, Igarashi T, Ando J.
    • Journal Title

      J Appl Physiol (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Furuse M. Identification of adherens junction-associated GTPase activating proteins by the fluorescence localization-based expression cloning.2008

    • Author(s)
      Matsuda M, Kobayashi Y, Masuda S, Adachi M, Watanabe T, Yamashita JK, Nishi E, Tsukita S,
    • Journal Title

      Exp Cell Res (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyperpolarization-activated cyclic nucleotide-gated channels and T-type calcium channels confer automaticity of embryonic stem cell-derived cardiomyocytes.2007

    • Author(s)
      Yanagi K, Takano M, Narazaki G, Uosaki H, Hoshino T, Ishii T, Misaki T, Yamashita JK*.
    • Journal Title

      Stem Cells 25

      Pages: 2712-2719

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration.2007

    • Author(s)
      Sone M, Itoh h, Yamahara K, Yamashita JK, 他16名
    • Journal Title

      Arterioscler Thromb Vasc Biol 27

      Pages: 2127-2134

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differentiation of arterial, venous, and lymphatic endothelial cells from vascular progenitors2007

    • Author(s)
      Yamashita JK*.
    • Journal Title

      Trends Cardiovasc Med 17

      Pages: 59-63

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two Populations of Thyl-Positive mesenchymal cells regulate the in vitro maturation of hepatic progenitor cells.2007

    • Author(s)
      Kamo N, (他7名) Yamashita JK, Kubo H, Ikai I.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 292

      Pages: 526-534

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differentiation stage-specific analysis of gene function with inducible short hair-pin RNA in differentiating embryonic stem cells.2006

    • Author(s)
      Hiraoka-Kanie M, Miyagishi M, Yamashita JK
    • Journal Title

      Biochem Biophys Res Commun 351

      Pages: 669-674

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Adrenomedullin/cyclic AMP pathway induces Notch activation and differentiation of arterial endothelial cells from vascular progenitors.2006

    • Author(s)
      Yurugi-Kobayashi T, Itoh H, Schroeder T, Nakano A, Narazaki G, Kita F, Yanagi K, Hiraoka-Kanie M, Inoue E, Ara T, Nagasawa T, Just U, Nakao K, Nishikana SI, Yamashita JK
    • Journal Title

      Arterioscler Thromb Vasc Biol 26

      Pages: 1977-1984

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Differentiation of lymphatic endothelial cells from embryonic stem cells on OP9 stromal cells.2006

    • Author(s)
      Kono T, Kubo H, Shimazu C, Ueda Y, Takahashi M, Yanagi K, Fujita N, Tsuruo T, Wada H, Yamashita JK
    • Journal Title

      Arterioscler Thromb Vasc Biol 26

      Pages: 2070-2076

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Azumamides A-E : Histone Deacetylase Inhibitory Cyclic Tetrapeptides from the Marine Sponge Mycale izuensis.2006

    • Author(s)
      Nakao Y, Yoshida S, Matsunaga S, Shindoh N, Terada Y, Nagai K, Yamashita JK, Ganesan A, Soest van RW, Fusetani N.
    • Journal Title

      Angew Chem Int Ed 45

      Pages: 7553-7557

    • Related Report
      2006 Annual Research Report
  • [Journal Article] TGF-beta signaling in embryonic stem cell-derived endothelial cells.2006

    • Author(s)
      Watabe T, Yamashita JK, Mishima K, Miyazono K
    • Journal Title

      Methods Mol Biol 330

      Pages: 341-351

    • Related Report
      2006 Annual Research Report
  • [Presentation] ES細胞を用いた新しい構成的アプローチによる血管分化多様化2007

    • Author(s)
      山下 潤
    • Organizer
      第30回日本分子生物学会ワークショップ「血管リンパ管研究の新展開」(オーガナイザー)
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] ES細胞を用いた構成的アプローチによる血管分化多様化機構の解析.2007

    • Author(s)
      山下 潤
    • Organizer
      日本血栓止血学会シンポジウム
    • Place of Presentation
      三重
    • Year and Date
      2007-11-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] Prospective identification of cardiac progenitors.2007

    • Author(s)
      Yamashita JK.
    • Organizer
      4th Annual Symposium of the American Heart Association Council on Basic Cardiovascular Sciences-Cardiovascular Repair and Regeneration. (Invited)
    • Place of Presentation
      Keystone, USA
    • Year and Date
      2007-07-30
    • Related Report
      2007 Annual Research Report
  • [Remarks] 京都大学 再生医科学研究所 附属幹細胞医学研究センター 幹細胞分化制御研究領域

    • URL

      http://www.frontier.kyoto-u.ac.jp/es02/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2018-03-28  

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