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

Research Project

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
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsエピゲノム制御 / 血管内皮細胞 / 細胞分化 / 転写因子 / ヒストン修飾 / 非翻訳RNA / GATA2
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.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (34 results)

All 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (24 results) (of which Invited: 1 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-seq.2014

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

      Kidney International

      Volume: 85 Issue: 1 Pages: 31-38

    • DOI

      10.1038/ki.2013.321

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.2014

    • Author(s)
      Maejima T, Inoue T, Kanki Y,,,,, Kodama T, Wada Y
    • Journal Title

      Plos One

      Volume: in press

    • NAID

      120006667792

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements.2014

    • Author(s)
      Inoue T, Kohro T, Tanaka T, Kanki Y, Li G, Poh HM, Mimura I, Kobayashi M, Taguchi A, Maejima T, Suehiro JI, Sugiyama A, Kaneki K, Aruga H, Dong S, Stevens JF, Yamamoto S, Tsutsumi S, Fujita T, Ruan X, Aburatani H, Nangaku M, Ruan Y, Kodama T, Wada Y.
    • Journal Title

      Genome Biology

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • 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 Issue: 11 Pages: 921-933

    • DOI

      10.1111/gtc.12086

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor associated macrophages2013

    • Author(s)
      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 Issue: 10 Pages: 3019-3028

    • DOI

      10.1158/0008-5472.can-12-3231

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] TNF alpha signals through specialized factories where responsive coding and miRNA genes are transcribed.2012

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

      The EMBO journal

      Volume: 31 Issue: 23 Pages: 4404-4414

    • DOI

      10.1038/emboj.2012.288

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • 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 KDM3A.2012

    • Author(s)
      Mimura I
    • Journal Title

      Mol Cell Biol.

      Volume: Aug;32(15) Issue: 15 Pages: 3018-3032

    • DOI

      10.1128/mcb.06643-11

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell.2012

    • 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, et al
    • Journal Title

      Nature Communications

      Volume: 6;3 Issue: 1 Pages: 883-883

    • DOI

      10.1038/ncomms1892

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 染色体立体構造網羅解析からの細胞特異性解読へのアプローチ2014

    • Author(s)
      神吉康晴
    • Organizer
      京都大学再生医科学研究所平成25年度共同研究報告会
    • Place of Presentation
      京都大学再生医科学研究所、京都市、日本
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] エピゲノム制御からの 新規血管新生因子の同定2014

    • Author(s)
      神吉康晴
    • Organizer
      第2回生活習慣病の分子細胞病態学研究会
    • Place of Presentation
      ホテル椿山荘東京、東京都、日本
    • Related Report
      2013 Annual Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] Transcription factor GATA2 is indispensable for the differentiation and maintenance of vascular endothelial cells2013

    • Author(s)
      Yasuharu Kanki, Taichi Matsunaga, Hiroyuki Aburatani, Youichiro Wada, Tatsuhiko Kodama, Jun Yamashita, Takashi Minami
    • Organizer
      The 11th Japan-Korea Joint Symposium on Vascular Biology
    • Place of Presentation
      Hyatt Regency jeju Hotel, Jeju Island, Korea
    • Related Report
      2013 Annual Research Report
  • [Presentation] Transcription factor GATA2 is indispensable for the differentiation and maintenance of vascular endothelial cells2013

    • Author(s)
      神吉康晴、興梠貴英、堤修一、三村維真理、松永太一、山水康平、片山志織、油谷浩幸、児玉龍彦、和田洋一郎、山下潤、南敬
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜、横浜市、日本
    • Related Report
      2013 Annual Research Report
  • [Presentation] A novel epigenetic mechanism revealed tumor associated angiogenesis2013

    • Author(s)
      Yasuharu Kanki, Jun-ichi Suehiro, Tsuyoshi Osawa, Imari Mimura, Youichiro Wada, Hiroyuki Aburatani, Tatsuhiko Kodama, Takashi Minami
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜市、日本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Three Dimensional Chromatin Architecture Correlates with Two Opposite Transcription Factors, which contributes the Cell Specificity2013

    • Author(s)
      Yasuharu Kanki
    • Organizer
      The 5th HOPE meeting
    • Place of Presentation
      グランドプリンスホテル新高輪
    • Related Report
      2012 Research-status Report
  • [Presentation] Comprehensive analyses revealed the epigenetic switch during the endothelial cell differentiation.2013

    • Author(s)
      Yasuharu Kanki, Taichi Matsunaga, Youichiro Wada, Jun Yamashita, Takashi Minami
    • Organizer
      第12回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Research-status Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] Epigenetically coordinated GATA2 bindings are necessary for the endothelial cell specificity2012

    • Author(s)
      Yasuharu Kanki, Takahide Kohro, Shuichi Tsutsumi, Imari Mimura, Takao Hamakubo, Takashi Minami, Youichiro Wada, Hiroyuki Aburatani, Tatsuhiko Kodama
    • Organizer
      第6回日本エピジェネティクス研究会年会
    • Place of Presentation
      東京都学術総合センター
    • Related Report
      2012 Research-status Report
  • [Presentation] ChIP-sequence Reveals Functional Interleukin-4-Inducible STAT6 Binding to the Vascular Cell Adhesion Molecule 1 Promoter2012

    • Author(s)
      Yasuharu KANKI
    • Organizer
      第12回東京大学生命科学シンポジウム
    • Place of Presentation
      東京大学
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulation of the Endothelial-Mesenchymal Transition (EndMT)2012

    • Author(s)
      YASUHARU KANKI, Shuing Jiang, Shuichi Tstsumi, Takahide Kohro, Imari Mimura, Tatsuhiko Kodama, Makoto Naito, Hiroyuki Aburatani, Takashi Minami
    • 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
    • Related Report
      2012 Research-status Report
  • [Presentation] ChIP-sequence Reveals Functional Interleukin-4-Inducible STAT6 Binding to the Vascular Cell Adhesion Molecule 1 Promoter2012

    • Author(s)
      Yasuharu Kanki
    • Organizer
      NGS現場の会第2回研究会
    • Place of Presentation
      大阪ホテル阪急エキスポパーク
    • Related Report
      2012 Research-status Report
  • [Presentation] The initiation step about the changes of transcription factor bindings and histone modifications is involved in sustained gene inductions.2012

    • Author(s)
      Yasuharu Kanki, Hideto Tozawa, Jun-ichi Suehiro, Shuichi Tsutsumi, Takahide Kohro, Hiroyuki Aburatani, Youichiro Wada, Takashi Minami, Takao Hamakubo, Tatsuhiko Kodama
    • Organizer
      Keystone Symposia 2013 Aging and Diseases of Aging
    • Place of Presentation
      Sheraton Miyako Hotel Tokyo
    • Related Report
      2012 Research-status Report
  • [Presentation] Epigenetic Switch on the Differentiation of Mouse Vascular Endothelial Cells2012

    • Author(s)
      Yasuharu KANKI, Kohei Yamamizu, Jun Yamashita
    • Organizer
      International Society for Stem Cell Research 10th Annual Meeting
    • Place of Presentation
      Pacifico Yokohama
    • Related Report
      2012 Research-status Report
  • [Presentation] Molecular mechanism about sustained VCAM-1 induction by the transcriptome and epigenomic analyses.2012

    • 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
    • Related Report
      2012 Research-status Report
  • [Presentation] Two transcription factors mediated opposite chromatin conformation correlates with endothelial cell specificity2012

    • Author(s)
      Yasuharu KANKI, Teppei Shimamura, Miyako Fujii, Imari Mimura, Tsuyoshi Inoue, Takao Hamakubo, Hiroyuki Aburatani, Satoru Miyano, Takashi Minami, Youichiro Wada, Tatsuhiko Kodama
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Research-status Report
  • [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
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [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
      特許
    • Acquisition Date
      2014-01-28
    • Related Report
      2013 Final Research Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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