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2013 Fiscal Year Final Research Report

Genetic and Epigenetic Landscape of Endothelial Cells Differentiation Reveal the Transcriptional Factors Network.

Research Project

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Project/Area Number 24710227
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field System genome science
Research InstitutionThe University of Tokyo

Principal Investigator

KANKI Yasuharu  東京大学, アイソトープ総合センター, 助教 (00534869)

Project Period (FY) 2012-04-01 – 2014-03-31
Keywordsエピゲノム制御 / 血管内皮細胞 / 細胞分化 / 転写因子
Research Abstract

In this report, our aim is to establish the more efficient and practical endothelial cell differentiation system from embryonic stem (ES) or induced pluripotent stem (iPS) cells. On this purpose, we analyzed the endothelial cell differentiation system from mouse ES cells by using two comprehensive analyses ChIP-seqs and micorarrays.
From these experiments we found out H3K4me3 have changed on early stage during differentiation. Moreover, we discovered some bivalent genes (H3K4me3 and H3K27me3 double positive) such as Etv2, Gata2, Sox18, Sox7 and Fli1 which are upregulated at early time points and supposed to be candidates for master regulators of endothelial cells differentiation. Knockdown of these factors caused drastic reduction of endothelial cell differentiation efficiency.
Taken together, these findings have suggested that determination of cell fate is based on not only master transcription factors but also epigenetic histone modifications.

  • Research Products

    (17 results)

All 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (9 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Revolution of nephrology research by deep sequencing : ChIP-seq and RNA-seq2014

    • Author(s)
      Mimura I, Kanki Y, Kodama T, Nangaku M
    • Journal Title

      Kidney Int

      Volume: 85(1) Pages: 31-38

    • DOI

      10.1038/ki.2013.321

    • Peer Reviewed
  • [Journal Article] GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation2013

    • Author(s)
      Suzuki M, Kobayashi-Osaki M, Tsutsumi S, Pan X, Ohmori S, Takai J, Moriguchi T, Ohneda O, Ohneda K, Shimizu R, Kanki Y, Kodama T, Aburatani H, Yamamoto M
    • Journal Title

      Genes Cells

      Volume: 18(11) Pages: 921-933

    • DOI

      10.1111/gtc.12086

    • Peer Reviewed
  • [Journal Article] Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor-associated macrophages2013

    • Author(s)
      Osawa T, Tsuchida R, Muramatsu M, Shimamura T, Wang F, Suehiro J, Kanki Y, Wada Y, Yuasa Y, Aburatani H, Miyano S, Minami T, Kodama T, Shibuya M
    • Journal Title

      Cancer Res

      Volume: 73(10) Pages: 3019-3028

    • DOI

      10.1158/0008-5472.CAN-12-3231

    • Peer Reviewed
  • [Journal Article] TNFαsignals through specialized factories where responsive coding and miRNA genes are transcribed2012

    • Author(s)
      Papantonis A, Kohro T, Baboo S, Larkin JD, Deng B, Short P, Tsutsumi S, Taylor S, Kanki Y, Kobayashi M, Li G, Poh HM, Ruan X, Aburatani H, Ruan Y, Kodama T, Wada Y
    • Journal Title

      EMBO J

      Volume: 31(23) Pages: 4404-4414

    • DOI

      10.1038/emboj.2012.288

    • Peer Reviewed
  • [Journal Article] Dynamic change of chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible factor 1 and KDM3A2012

    • Author(s)
      Mimura I, Nangaku M, Kanki Y, Tsutsumi S, Inoue T, Kohro T, Yamamoto S, Fujita T, Shimamura T, Suehiro J, Taguchi A, Kobayashi M, Tanimura K, Inagaki T, Tanaka T, Hamakubo T, Sakai J, Aburatani H, Kodama T, Wada Y
    • Journal Title

      Mol Cell Biol

      Volume: 32(15) Pages: 3018-3032

    • DOI

      10.1128/MCB.06643-11

    • Peer Reviewed
  • [Journal Article] Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell2012

    • Author(s)
      Yae T, Tsuchihashi K, Ishimoto T, Motohara T, Yoshikawa M, Yoshida GJ, Wada T, Masuko T, Mogushi K, Tanaka H, Osawa T, Kanki Y, Minami T, Aburatani H, Ohmura M, Kubo A, Suematsu M, Takahashi K, Saya H, Nagano O
    • Journal Title

      Nat Commun

      Volume: 3 Pages: 883

    • DOI

      10.1038/ncomms1892

    • Peer Reviewed
  • [Presentation] A novel epigenetic mechanism revealed tumor associated angiogenesis2013

    • Author(s)
      神吉 康晴
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、神奈川県
    • Year and Date
      20131003-05
  • [Presentation] Transcription factor GATA2 is indispensable for the differentiation and maintenance of vascular endothelial cells2013

    • Author(s)
      神吉 康晴
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜、神奈川県
    • Year and Date
      20130911-13
  • [Presentation] Transcription factor GATA2 is indispensable for the differentiation and maintenance of vascular endothelial cells2013

    • Author(s)
      Yasuharu Kanki
    • Organizer
      The 11th Japan-Korea Joint Symposium on Vascular Biology
    • Place of Presentation
      Hyatt Regency Jeju Hotel, Korea
    • Year and Date
      20130821-24
  • [Presentation] Comprehensive analyses revealed the epigenetic switch during the endothelial cell differentiation2013

    • Author(s)
      神吉 康晴
    • Organizer
      第12回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜、神奈川県
    • Year and Date
      20130321-23
  • [Presentation] Two transcription factors mediated opposite chromatin conformation correlates with endothelial cell specificity2012

    • Author(s)
      神吉 康晴
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場、福岡県
    • Year and Date
      20121211-14
  • [Presentation] Molecular mechanism about sustained VCAM-1 induction by the transcriptome and epigenomic analyses2012

    • Author(s)
      Yasuharu Kanki
    • Organizer
      第20回日本血管生物医学会学術集会(The 10th Korea-Japan Joint Symposium on Vascular Biology)
    • Place of Presentation
      徳島あわぎんホール、徳島県
    • Year and Date
      20121205-07
  • [Presentation] The initiation step about the changes of transcription factor bindings and histone modifications is involved in sustained gene inductions2012

    • Author(s)
      Yasuharu Kanki
    • Organizer
      Keystone Symposia 2013 Aging and Diseases of Aging
    • Place of Presentation
      Miyako Hotel Tokyo、東京都
    • Year and Date
      20121022-27
  • [Presentation] Regulation of the Endothelial-Mesenchymal Transition (EndMT)2012

    • Author(s)
      Yasuharu Kanki
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館、北海道
    • Year and Date
      20120919-21
  • [Presentation] Epigenetic Switch on the Differentiation of Mouse Vascular Endothelial Cells2012

    • Author(s)
      Yasuharu Kanki
    • Organizer
      International Society for Stem Cell Research 10th Annual Meeting
    • Place of Presentation
      Pacifico Yokohama、神奈川県
    • Year and Date
      20120613-16
  • [Book] 血管医学2013

    • Author(s)
      神吉康晴
    • Total Pages
      9
    • Publisher
      メディカルレビュー社
  • [Patent(Industrial Property Rights)] 血管内皮細胞の活性化に起因する疾患の治療又は予防剤2014

    • Inventor(s)
      南 敬, 神吉 康晴, 末弘 淳一
    • Industrial Property Rights Holder
      東京大学TLO/JST
    • Industrial Property Rights Type
      PCT
    • Industrial Property Number
      JP2014/051830
    • Acquisition Date
      2014-01-28
    • Overseas

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Published: 2015-06-25  

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