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Elucidation of the formation and the maintenance of hematopoietic cell clusters, which contain hematopoietic stem cells, along with endothelial cells of the dorsal aorta in midgestation mouse embryos

Research Project

Project/Area Number 26440118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Nobuhisa Ikuo  東京医科歯科大学, 難治疾患研究所, 准教授 (40332879)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsAGM / Hematopoiesis / Sox17 / Notch1 / VE-Cad / hematopoiesis / hamatopoiesis / Hes1
Outline of Final Research Achievements

During mouse development, hematopoietic stem cells (HSCs) firstly arise intra-aortic cell clusters (IAHCs) of the dorsal aorta at embryonic day 10.5. Introduction of transcription factor Sox17 into cells of IAHCs leads to consistent formation of cell clusters containing HSCs in vitro. We examined the molecular mechanism of this phenomenon in this project. We showed the importance of the thrombopoietin/c-Mpl signal pathway in Sox17-transduced hematopoietic cell clusters. Moreover, we demonstrated that the binding of Sox17 to the Notch1 promoter induced the Notch1-expression and Notch1 intra-cellular domain (NICD, the active form)-transduced cells maintained the undifferentiated state. Cells transduced with Hes1, which is one of the target genes of the Notch signaling pathway, have a capacity to maintain the undifferentiated state. Furthermore, the Sox17-induced adherent molecule vascular endothelial cadherin has a role of the formation and the maintenance of hematopoietic cell clusters.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (20 results)

All 2017 2016 2015 2014 Other

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 4 results) Remarks (2 results)

  • [Journal Article] Thrombopoietin contributes to the formation and the maintenance of hematopoietic progenitor-containing cell clusters in the aorta-gonad-mesonephros region.2017

    • Author(s)
      Harada K, Nobuhisa I, Anani M, Saito K, and Taga T
    • Journal Title

      Cytokine

      Volume: 95 Pages: 35-42

    • DOI

      10.1016/j.cyto.2017.02.012

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A synthetic polymer scaffold reveals the self-maintenance strategies of rat glioma stem cells by organization of the advantageous niche.2016

    • Author(s)
      Tabu K, Muramatsu N, Mangani C, Wu M, Zhang R, Kimura T, Terashima K, Bizen N, Kimura R, Wang W, Murota Y, Kokubu Y, Nobuhisa I, Kagawa T, Kitabayashi I, Bradley M, Taga T.
    • Journal Title

      Stem Cells

      Volume: 34 Issue: 5 Pages: 1151-1162

    • DOI

      10.1002/stem.2299

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Induction of protumoral CD11c[high] macrophages by glioma cancer stem cells thorough GM-CSF2016

    • Author(s)
      Kokubu et al
    • Journal Title

      Genes to Cells

      Volume: 21 Issue: 3 Pages: 241-251

    • DOI

      10.1111/gtc.12333

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sox17-ediated Maintenance of Fetal Intra-ortic Hematopoietic Cell Clusters2014

    • Author(s)
      Nobuhisa. Ikuo., Ozawa. M., Uemura. M., Kishikawa. Y., Azumi. M. Harada K. Takagi M Saito. K., Kanai-Azuma M. Kanai. Y Iwama. A. Tetsuya.
    • Journal Title

      MCB

      Volume: (印刷中) Issue: 11 Pages: 1976-90

    • DOI

      10.1128/mcb.01485-13

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sox17 as a candidate regulator of myeloid restricted differentiation potential.2014

    • Author(s)
      Anani M, Nobuhisa I, Osawa M, Iwama A, Harada K, Saito K, Taga T
    • Journal Title

      Dev. Growth Differ.

      Volume: 56 Issue: 6 Pages: 469-479

    • DOI

      10.1111/dgd.12147

    • NAID

      40020174678

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Maintenance of hematopoietic stem and progenitor cell phenotype of intra-aortic cell clusters in the AGM region through the Sox17-Notch1-Hes1 axis.2016

    • Author(s)
      齋藤清香, 信久幾夫, Anani Maha, 原田果歩, 髙橋聡美, Lickert Heiko, 金井正美, 金井克晃, 田賀哲也.
    • Organizer
      第39回分子生物学会年会
    • Place of Presentation
      パシフィッコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Involvement of transcription factor Sox17-mediated expression of adhesion molecules in hematopoietic cell cluster formation in midgestation mouse dorsal aorta.2016

    • Author(s)
      髙橋聡美, 信久幾夫, 齋藤清香, 田賀哲也.
    • Organizer
      第39回分子生物学会年会
    • Place of Presentation
      パシフィッコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mechanism of maintaining hematopoietic stem and progenitor cell phenotype of intra-aortic cell clusters in the AGM region through the Sox17- Notch1-Hes1 axis.2016

    • Author(s)
      齋藤清香, 信久幾夫, Anani M, 原田果歩, 髙橋聡美, 田賀哲也.
    • Organizer
      第14回幹細胞シンポジウム
    • Place of Presentation
      淡路夢舞台(兵庫県・淡路市)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] Maintenance of hematopoietic stem and progenitor cell phenotype of intra-aortic cell clusters in the AGM region as a site of definitive hematopoiesis through the Sox17-Notch1-Hes1 axis2015

    • Author(s)
      Saito et al
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアアイランド (兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Sox17 maintains the stem cell population of intra-aortic hematopoietic cell clusters in the aorta-gonad-mesonephros region through Notch signaling2015

    • Author(s)
      Nobuhisa et al
    • Organizer
      The 44th Annual Meeting of The Japanese Society for Immunology
    • Place of Presentation
      Sapporo Convention Center, Hokkaido, Sapporo
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sox17 is critical for the maintenance of stem cell phenotype of intra-aortic hematopoietic clusters of cells in the aorta-gonad-mesonephros region2015

    • Author(s)
      Nobuhisa et al
    • Organizer
      International Society for Experimental Hematology 44th Annual Scientific Meeting
    • Place of Presentation
      The Kyoto International Conference, Kyoto
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Maintenance of hematopoietic stem and progenitor cell phenotype of intra-aortic cell clusters in the AGM region through the Sox17-Notch1-Hes1 axis2015

    • Author(s)
      Saito et al
    • Organizer
      International Society for Experimental Hematology 44th Annual Scientific Meeting
    • Place of Presentation
      The Kyoto International Conference, Kyoto
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sox17 maintains the stem cell population of intra-aortic hematopoietic cell clusters in the aorta-gonad-mesonephros region2015

    • Author(s)
      Nobuhisa I and Taga T
    • Organizer
      The 10th International Symposium of the Institute Network
    • Place of Presentation
      Furate Hall, Hokkaido, Sapporo
    • Year and Date
      2015-07-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Maintenance of intra-aortic hematopoietic cell clusters in the AGM region through the Sox17-Notch1-Hes1 axis2015

    • Author(s)
      Saito et al
    • Organizer
      第13回幹細胞シンポジウム
    • Place of Presentation
      伊藤国際学術研究センター (東京都・文京区)
    • Year and Date
      2015-05-29
    • Related Report
      2015 Research-status Report
  • [Presentation] Sustained expression of Sox17 in AGM-derived hematopoietic stem/progenitor cells maintain the self-renewal capacity and the hematopoietic ability to produce myeloid progenitors2014

    • Author(s)
      Anani M, Nobuhisa I, Osawa M, Iwama A, Harada K, Saito K, Taga T
    • Organizer
      The 43rd Annual Meeting of The Japanese Society for Immunology
    • Place of Presentation
      京都国際会議場(京都府・京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Role of the Notch signaling pathway and its downstream genes in hematopoietic progenitor cell-containing cell clusters in the aorta-gonad-mesonephros region2014

    • Author(s)
      Saito K, Nobuhisa I, Anani M, Harada K, Taga T
    • Organizer
      The 37th Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      パシフィッコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Sustained expression of Sox17 in the aorta-gonad-mesonephros-derived hematopoietic cells maintain the self-renewal capacity and the hematopoietic ability to produce myeloid progenitors2014

    • Author(s)
      Nobuhisa I, Anani M, Osawa M, Iwama A, Harada K, Saito K, Taga T
    • Organizer
      The 37th Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      パシフィッコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Sox17-transduction imparts fetal hematopoietic cells with the myeloid-restricted differentiation potential2014

    • Author(s)
      Anani M, Nobuhisa I, Osawa M, Iwama A, Harada K, Saito K, and Taga T
    • Organizer
      The 12th Stem Cell Research Symposium
    • Place of Presentation
      九州大学医学部百年講堂(福岡県・福岡市)
    • Year and Date
      2014-05-30 – 2014-05-31
    • Related Report
      2014 Research-status Report
  • [Remarks] 東京医科歯科大学 難治疾患研究所 幹細胞制御分野

    • URL

      http://www.tmd.ac.jp/mri/scr/index.html

    • Related Report
      2016 Annual Research Report 2015 Research-status Report 2014 Research-status Report
  • [Remarks] (プレスリリース)胎生期の造血幹細胞の維持に関与する分子Sox17の発見

    • URL

      http://www.tmd.ac.jp/archive-tmdu/kouhou/20140423.pdf

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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