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Molecular and cellular analyses of hematopoietic stem cell damage induced by low dose-rate irradiation

Research Project

Project/Area Number 16H02955
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionHiroshima University

Principal Investigator

Takihara Yoshihiro  広島大学, 原爆放射線医科学研究所, 名誉教授 (60226967)

Co-Investigator(Kenkyū-buntansha) 大野 芳典  広島大学, 原爆放射線医科学研究所, 助教 (10548986)
安永 晋一郎  福岡大学, 医学部, 教授 (50336111)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords低線量放射線被ばく / 造血幹細胞 / 長期骨髄再構築能 / 多分化能 / 低線量率放射線被ばく / 低線量被ばく
Outline of Final Research Achievements

Hematopoietic tissues are highly sensitive to radiation and prone to radiation injury. It is feared that hematopoietic failure develops and, as a result of the later effects, hematopoietic abnormalities such as leukemia could be induced. We have analyzed effects of low dose-rate radiation exposure on hematopoietic tissues, that have largely remained elusive, and aimed to contribute for establishing a basic theory for preventing the adverse effects of low dose-rate exposure. We found that low dose-rate radiation exposure specifically decreased the number and activity of immature hematopoietic cells including hematopoietic stem cells. We then detailed the mechanism underlying the decrease at the molecular and cellular levels, further at the single cell level. Not only DNA repair responses against the genome damage but also apoptosis and cellular differentiation were induced in immature hematopoietic cells, which may give rise to specific reduction of immature hematopoietic cells.

Academic Significance and Societal Importance of the Research Achievements

本研究では、今まで充分には明らかにされて来なかった低線量率放射線被ばくの造血システムへの影響について細胞レベルから分子レベルまで詳細に解析した。原発作業や宇宙開発などの環境下では、長期間に渡る低線量率放射線被ばくが生ずることが危惧され、本研究で明らかにしたように造血幹細胞の特異的な減少や機能障害によって造血不全や免疫不全が引き起こされる危険性が考えられる。本研究成果を基に、低線量率放射線被ばくによって造血幹細胞障害が引き起こされるメカニズムが更に明らかにされ、新たな防御法の開発に道が開かれることを期待したい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (25 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (20 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] BMI1 controls transit amplification in chondrogenesis by preventing replication and transcription fork collision.2019

    • Author(s)
      Spaapen F, Eijssen L, Welting T, Prickaerts P, Salvaing J, Dahlmans V, Surtel D A M, Kruitz F, Kuijer R, Takihara Y, Wouters B G, Vidal M, Voncken J.W.
    • Journal Title

      Epigenomes

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A revised road map for the commitment of human cord blood CD34-negative hematopoietic stem cells2018

    • Author(s)
      Sumide Keisuke、Matsuoka Yoshikazu、Kawamura Hiroshi、Nakatsuka Ryusuke、Fujioka Tatsuya、Asano Hiroaki、Takihara Yoshihiro、Sonoda Yoshiaki
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2202-2202

    • DOI

      10.1038/s41467-018-04441-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A revised map for the commitment of human CD34-negative hematopoietic stem cells.2018

    • Author(s)
      Sumide, K., Matsuoka, Y., Kawamura, H., Nakatsuka, T., Fujioka, T., Asano, H., Takihara, Y., Sonoda, Y.
    • Journal Title

      Nature Communications

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PRC1 prevents replication stress during chondrogenic transit amplification2017

    • Author(s)
      Spaapen, F., Eijssen, L.M., Adriaens, M.E., Welting, T.J., Prickaerts, P., Salvaing, J., Dahlmans, V.E.H., Surtel, D.A.M., Kruitz, F., Kuijer, R., Takihara, Y., Marks, H., Stunnenberg, H.G., Wouters, B.G., Vidal, M., Voncken, J.W.
    • Journal Title

      Epigenomes

      Volume: 1(3) Issue: 3 Pages: 22-22

    • DOI

      10.3390/epigenomes1030022

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 骨髄の組織反応2017

    • Author(s)
      大野 芳典、竹立 恭子、白須 直人、安永 晋一郎、瀧原 義宏
    • Journal Title

      放射線生物研究

      Volume: 52(4) Pages: 336-349

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 低線量率放射線が造血幹細胞活性に与える影響2018

    • Author(s)
      大野 芳典, 竹立 恭子, 郭 芸, 菅野 雅元、白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      中国地区放射線影響研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effect of low dose-rate irradiation on the hematopoietic stem cells.2018

    • Author(s)
      大野 芳典, 竹立 恭子, 郭 芸, 菅野 雅元、白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第80回日本血液学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 低線量率放射線による造血幹細胞の機能低下とその分子機序2018

    • Author(s)
      大野 芳典, 竹立 恭子, 山藤 幹茂子, 郭 芸, 菅野 雅元、白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第61回日本放射線影響学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 造血における低線量率放射線に対する分子応答2018

    • Author(s)
      大野 芳典, 竹立 恭子, 山藤 幹茂子, 郭 芸, 菅野 雅元、白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 幹細胞活性制御因子Gemininの白血病の病態制御における役割2018

    • Author(s)
      大野 芳典, 竹立 恭子, 白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第22回 造血器腫瘍研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effect of low dose-rate irradiation on the hematopoietic stem cells2017

    • Author(s)
      Ohno, Y., Shirasu, N., Suzuki-Takedachi, K., Santo, M., Guo, Y., Kanno, M., Yasunaga, S., Ohtsubo, M., Takihara, Y.
    • Organizer
      The 1st International Symposium of the network-type Joint Usage/ Research Center for Radiation Disaster Medical Science
    • Place of Presentation
      Hiroshima, Japan
    • Year and Date
      2017-02-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular response for low dose-rate irradiation in the hematopoietic system2017

    • Author(s)
      大野 芳典, 竹立 恭子, 郭 芸, 菅野 雅元, 白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第15回幹細胞シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低線量率放射線被ばくに対する造血システムの分子応答2017

    • Author(s)
      大野 芳典, 竹立 恭子, 郭 芸, 菅野 雅元, 白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第58回原爆後障害研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Molecular responses for low dose-rate irradiation in the hematopoietic stem cells.2017

    • Author(s)
      大野 芳典, 竹立 恭子, 郭 芸, 菅野 雅元, 白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第79回 日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低線量率放射線照射環境下における造血システムへの影響とその分子応答2017

    • Author(s)
      大野 芳典, 竹立 恭子, 郭 芸, 菅野 雅元、白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第60回 日本放射線影響学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 造血幹細胞の細胞周期と分化を制御する中核因子Geminin2017

    • Author(s)
      大野 芳典, 竹立 恭子, 白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第21回バイオ治療法研究会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膜透過型ペプチドを用いた幹細胞活性制御因子Gemininの発現制御法の開発2017

    • Author(s)
      竹立 恭子, 大野 芳典, 白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第21回バイオ治療法研究会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 造血幹細胞の細胞周期制御と分化制御における分子機能2017

    • Author(s)
      竹立 恭子, 大野 芳典, 白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低線量率放射線が造血に与える影響2017

    • Author(s)
      大野 芳典, 竹立 恭子, 白須 直人, 安永 晋一郎, 大坪 素秋, 瀧原 義宏
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 造血幹細胞の低線量率放射線被ばくに対する分子応答の解析2016

    • Author(s)
      大野 芳典、鈴木-竹立 恭子、山藤 幹茂子、郭 芸、菅野 雅元、白須 直人、大坪 素秋、仲 一仁、安永 晋一郎、瀧原 義宏
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低線量率被ばくに対する造血幹細胞の分子応答の解析2016

    • Author(s)
      大野芳典、竹立恭子、山藤幹茂子、郭芸、菅野雅元、白須直人、安永晋一郎、大坪素秋、仲一仁
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      広島
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 造血システムに対する放射線被ばくの影響2016

    • Author(s)
      瀧原義宏
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      広島
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Low dose-rate irradiation specifically affects hematopoietic stem cells.2016

    • Author(s)
      Ohno, Y., Suzuki-Takedachi, K., Santo, M., Guo, Y., Kanno, M., Yasunaga, S., Ohtsubo, M., Naka, K., Takihara, Y.
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] Low dose-rate irradiation specifically affects hematopoietic stem cells2016

    • Author(s)
      Takihara, Y., Ohno, Y., Suzuki-Takedachi, K., Santo M., Yasunaga, S., Ohtsubo, M., Naka, K.
    • Organizer
      45th Annual Scientific Meeting of the International Society of Experimental Hematology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2016-08-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of low dose-rate irradiation on the hematopoietic system.2016

    • Author(s)
      Ohno, Y., Suzuki-Takedachi, K., Santo, M., Guo, Y., Kanno, M., Yasunaga, S., Ohtsubo, M., Naka, K., Takihara, Y.
    • Organizer
      The 14th Stem Cell Research Symposium
    • Place of Presentation
      Awaji, Japan
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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