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Elucidation of mechanisms for development, maturation, and maintenance in hematopoietic stem cells of intra-aortic hematopoietic cell clusters at midgestated mouse embryos

Research Project

Project/Area Number 18K06249
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44020:Developmental biology-related
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) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords造血幹細胞 / 転写因子 / 血液細胞塊 / Sox17 / 胎仔 / AGM / Gimap / hematopoietic stem cells / 造血 / NF-kappaB / Tet1 / 発生
Outline of Final Research Achievements

Hematopoietic stem cells, which are the source of all blood cells, first arise in hematopoietic cell clusters of the dorsal aorta in the embryonic day 10.5 of the mouse embryo. We analyzed genes and signaling pathways induced by Sox17, a transcription factor involved in the development, maturation and maintenance of hematopoietic stem cells in midgestation mouse embryos. We investigated the involvement of adherent molecules ESAM, the GTPase Gimap6, the signaling pathway activating NF-kappaB, and TET1 involved in DNA methylation, respectively.

Academic Significance and Societal Importance of the Research Achievements

今回得られたマウス胎生中期における大動脈内腔の造血幹細胞を含む血液細胞塊の形成・成熟・維持にかかわる分子およびシグナル経路をさらに解析していくことにより、生体の造血幹細胞の特性と比較することにより、培養皿上での造血幹細胞の形成および維持機構の解明につながることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2020 2019 2018 Other

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Glioma stem cell (GSC)-derived autoschizis-like products confer GSC niche properties involving M1-like tumor-associated macrophages2020

    • Author(s)
      Tabu K, Liu W, Kosaku A, Terashima K, Murota Y, Aimaitijiang A, Nobuhisa I, Hide T and Taga T
    • Journal Title

      Stem Cells

      Volume: - Issue: 8 Pages: 921-935

    • DOI

      10.1002/stem.3193

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sox17-mediated expression of adherent molecules is required for the maintenance of undifferentiated hematopoietic cluster formation in midgestation mouse embryos2020

    • Author(s)
      Takahashi Satomi、Nobuhisa Ikuo、Saito Kiyoka、Gerel Melig、Itabashi Ayumi、Harada Kaho、Osawa Mitsujiro、Endo Takaho A.、Iwama Atsushi、Taga Tetsuya
    • Journal Title

      Differentiation

      Volume: 115 Pages: 53-61

    • DOI

      10.1016/j.diff.2020.08.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway2020

    • Author(s)
      Anani Maha、Nobuhisa Ikuo、Taga Tetsuya
    • Journal Title

      Journal of Cancer Prevention

      Volume: 25 Issue: 4 Pages: 204-212

    • DOI

      10.15430/jcp.2020.25.4.204

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Maintenance of hematopoietic stem and progenitor cells in fetal intra-aortic hematopoietic clusters by the Sox17-Notch1-Hes1 axis.2018

    • Author(s)
      Saito K, Nobuhisa I, Harada K, Takahashi S, Anani M, Lickert H, Kanai-Azuma M, Kanai Y, Taga T.
    • Journal Title

      Exp Cell Res

      Volume: 365 Issue: 1 Pages: 145-155

    • DOI

      10.1016/j.yexcr.2018.02.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 胎生中期マウス内動脈内腔における転写因子Sox17を介したGIMAP6発現の造血能に対する寄与2020

    • Author(s)
      信久幾夫, 塚原涼太,齋藤清香, 金井克晃, 金井正美, 田賀哲也
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Role of the Rasip1 in the hematopoiesis of HSC-containing hematopoietic cluster cells in midgestation of mouse embryos2020

    • Author(s)
      Melig G, Nobuhisa I, Kiyoka S, Tsukahara R, Itabashi A, Kanai Y, Kanai M, Taga T
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウス胎仔肝臓・成体骨髄の造血幹細胞を含む細胞集団への転写因子Sox17強制発現による細胞塊形成と未分化性維持2020

    • Author(s)
      板橋歩未、信久幾夫、横居優貴、齋藤清香、塚原涼太、Melig Gerel、田賀哲也
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Contribution of Rasip1 to the maintenance of hematopoietic activity of cluster-forming cells in midgestation mouse embryos2020

    • Author(s)
      Melig G, Nobuhisa I, Kiyoka S, Tsukahara R, Itabashi A, Kanai Y, Kanai M, Taga T
    • Organizer
      第43回分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 転写因子Sox17を導入した造血幹・前駆細胞の細胞塊形成能は発生の進行に伴い低下する2020

    • Author(s)
      板橋歩未、信久幾夫、横居優貴、齋藤清香、塚原涼太、Melig Gerel、田賀哲也
    • Organizer
      第43回分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Systematic analysis of brain pH and lactate levels in animal models: relationships and implications for behavioral outcomes2019

    • Author(s)
      Hagihara H, Shoji H, Kohno T, Hayata A, Tamada K, Hori K, Tatsukawa T, Shibutani M, Wakatsuki S, Hagino Y, Kasahara T, Numakawa T, Ohtabi H, Nobuhisa I, et al.
    • Organizer
      The 21st Annual Meeting of the International Behavioural and Neural Genetics Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enhanced erythropoiesis in bone marrow of C6 glioma-bearing mice2019

    • Author(s)
      Aimaitijiang A, Tabu K, Wang W, Nobuhisa I and Taga T.
    • Organizer
      The 17th Stem Cell Research Sympodium
    • Related Report
      2019 Research-status Report
  • [Presentation] The role of GIMAP family in the maintenance of hematopoietic capacity in hematopoietic cell cluster in midgestation mouse dorsal aorta2019

    • Author(s)
      Tsukahara Y, Nobuhisa I, Saito K, Kanai Y, Kanai M, and Taga T
    • Organizer
      The 42th Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2019 Research-status Report
  • [Presentation] Involvement of TET1 in the maintenance of the hematopoietic capacity in hematopoietic cell clusters in the dorsal aorta in midgestation mouse embryo2019

    • Author(s)
      Nobuhisa I, Saito K, Tsukahara R, Azuma K, Melig G, Itabashi A, Taga T
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Research-status Report
  • [Presentation] Expression of TET family members in hematopoietic stem cell-containing clusters of the dorsal aorta in midgestation mouse embryo.2018

    • Author(s)
      Nobuhisa I, Saito K, and Taga T
    • Organizer
      The 16th Stem Cell Research Symposium
    • Related Report
      2018 Research-status Report
  • [Presentation] 成体型造血が出現する胎生期AGM 領域の未分化 血液細胞塊におけるエピジェネティック因子TET 1の役割2018

    • Author(s)
      東康哉、信久幾夫、斎藤清香、飯塚直樹、田賀哲也
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] マウス胎生中期の大動脈内腔に存在する造血幹細胞 含有細胞塊の未分化状態維持におけるNF-κ B シグナルの寄与2018

    • Author(s)
      飯塚直樹、信久幾夫、齋藤清香、東康哉、田賀哲也
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] マウス胎生中期AGM 領域におけるTet ファミリー遺伝子の発現解析2018

    • Author(s)
      齋藤清香、信久幾夫、田賀哲也
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] The contribution of TET1 to the maintenance of the hematopoietic capacity in hematopoietic stem cell-containing clusters in the dorsal aorta in midgestation mouse embryo2018

    • Author(s)
      Nobuhisa I, Saito K, Azuma K, Iizauka N, and Taga T
    • Organizer
      The 47th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2018 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

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

    • Related Report
      2020 Annual Research 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
      2019 Research-status Report 2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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