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Basic research on regulatory system for self-renewal and differentiation of hematopoietic stem cells for the purpose of future application to regenerative medicine

Research Project

Project/Area Number 26501004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Regenerative medicine
Research InstitutionFukuoka University (2015-2016)
Hiroshima University (2014)

Principal Investigator

YASUNAGA Shin'ichiro  福岡大学, 医学部, 教授 (50336111)

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)
瀧原 義宏  広島大学, 原爆放射線医科学研究所, 教授 (60226967)
Research Collaborator TAKEDACHI Kyoko (SUZUKI Kyoko)  広島大学, 原爆放射線医科学研究所, 技術職員
Sato MIMOKO  広島大学, 原爆放射線医科学研究所, 技術職員
KUROGI Toshiaki  広島大学, 原爆放射線医科学研究所, 技術職員
YAMADA Hiromi  福岡大学, 医学部, 技術職員
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)
Keywords再生医学 / 造血幹細胞 / 自己複製 / 細胞周期 / 細胞増殖 / 細胞分化 / Geminin / ユビキチン化
Outline of Final Research Achievements

Geminin regulates both of self-renewal and quiescence maintenance of hematopoietic stem cells (HSCs), and is a candidate key molecule for HSC regulation. Therefore, sophisticated manipulation of Geminin expression and function may be able to control HSC activity. In this study, we sorted out quiescent HSCs and self-renewing HSCs from bone marrow cells derived from Geminin-EYFP knock-in mice and examined difference in their gene expression at single cell level. In addition, we generated recombinant Geminin protein with membrane-translocating motif for easy induction and withdraw of Geminin expression in hematopoietic cells.

Report

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

    (40 results)

All 2017 2016 2015 2014 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (23 results) (of which Int'l Joint Research: 2 results) Book (2 results) Remarks (5 results)

  • [Journal Article] Is a bare-metal stent still useful for improving the outcome of percutaneous coronary intervention? From the FU-Registry2017

    • Author(s)
      GONDO, K., IKE, A., OGAWA, M., SHIRAI, K., SUGIHARA, M., NISHIKAWA, H., IWATA, A., KAWAMURA, A., MORI, K., ZHANG, B., MIURA, S., YASUNAGA, S. & SAKU, K.
    • Journal Title

      J Cardiol

      Volume: 69 Issue: 4 Pages: 652-659

    • DOI

      10.1016/j.jjcc.2016.06.009

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Manipulation of cell cycle and chromatin configuration by means of cell-penetrating Geminin.2016

    • Author(s)
      Ohno Y., Suzuki-Takedachi K., Yasunaga S., Kurogi T., Santo M., Masuhiro Y., Hanazawa S., Ohtsubo M., Naka K. & Takihara Y.
    • Journal Title

      PLoS ONE

      Volume: 11(5) Issue: 5 Pages: 1-14

    • DOI

      10.1371/journal.pone.0155558

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs)2016

    • Author(s)
      YASUNAGA, S., OHNO, Y., SHIRASU, N., ZHANG, B., SUZUKI-TAKEDACHI, K., OHTSUBO, M. & TAKIHARA, Y.
    • Journal Title

      Int J Hematol

      Volume: 104 Issue: 3 Pages: 324-9

    • DOI

      10.1007/s12185-016-2060-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Duplex PCR-RFLP for the simultaneous genotypeing of single nucleotide polymerisms in ADH1B abd ALDH2 genes.2016

    • Author(s)
      Shirasu N. & Yasunaga S.
    • Journal Title

      Anal. Sci.

      Volume: 32(12) Pages: 1363-1366

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-tumor Effect of Intravenous Administration of CRM197 for Triple-negative Breast Cancer Therapy.2016

    • Author(s)
      Nam S.O., Yotsumoto F., Miyata K., Fukagawa S., Odawara T., Manabe S., Ishikawa T,. Kuroki M., Yasunaga S. & Miyamoto S.
    • Journal Title

      Anticanceer Res.

      Volume: 36(7) Pages: 3651-3657

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significance of ACADM mutations identified from newborn screening of MCAD deficiency in Japan2016

    • Author(s)
      Keiichi Hara, Go Tajima, Satoshi Okada, Miyuki Tsumura, Reiko Kagawa, Kenichiro Shirao, Yoshinori Ohno, Shin'ichiro Yasunaga, Motoaki Ohtsubo, Ikue Hata, Nobuo Sakura, Yosuke Shigematsu, Yoshihiro Takihara, Masao Kobayashi
    • Journal Title

      Molecular Genetics and Metabolism

      Volume: 118 Issue: 1 Pages: 9-14

    • DOI

      10.1016/j.ymgme.2015.12.011

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Gemininによる白血病幹細胞の制御2015

    • Author(s)
      安永晋一郎、大野芳典、瀧原義宏
    • Journal Title

      日本臨床

      Volume: 73(5) Pages: 800-805

    • Related Report
      2015 Research-status Report
  • [Journal Article] Mosaicism of an ELANE mutation in an asymptomatic mother in a familial case of cyclic neutropenia.2015

    • Author(s)
      Hirata O, Okada S, Ttsumura M, Karakawa S, Matsumura I, Kimura Y, Mihara T, Yasunaga S, Takihara Y, Ohara O, Kobayashi M
    • Journal Title

      Journal of Clinical Immunology

      Volume: 2015 Issue: 5 Pages: 1-5

    • DOI

      10.1007/s10875-015-0165-1

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription of the Geminin gene is regulated by a negative-feedback loop.2014

    • Author(s)
      Ohno, Y., Saeki, K., Yasunaga, S., Kurogi. T., Suzuki-Takedachi, K., Shirai, M., Mihara K., Yoshida, K., Voncken J. W, Ohtsubo, M. & Takihara Y.
    • Journal Title

      Mol. Biol. Cel

      Volume: 25(8) Issue: 8 Pages: 1374-1383

    • DOI

      10.1091/mbc.e13-09-0534

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simple diagnosis of STAT1 gain-of-function alleles in patients with chronic mucocutaneous candidiasis.2014

    • Author(s)
      Mizoguchi Y, Tsumura M, Okada S, Hirata O, Minegishi S, Imai K, Hyakuna N, Muramatsu H, Kojima S, Ozaki Y, Imai T, Takeda S, Okazaki T, Ito T, Yasunaga S, Takihara Y, Bryant VL, Kong XF, Cypowyj S, Boisson-Dupuis S, Puel A, Casanova JL, Morio T, Kobayashi M.
    • Journal Title

      J. Leukoc. Biol.

      Volume: 95 Issue: 4 Pages: 667-76

    • DOI

      10.1189/jlb.0513250

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Effect of low dose-rate irradiation on the hematopoietic system.2017

    • 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] 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回日本分子生物学年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mechanism of anticancer effect on sonodynamic therapy in combination with DEG and microtubules.2016

    • Author(s)
      Shibaguchi H., Shirasu N., Kuroki M., Yasunaga S.
    • Organizer
      The 75th Annual Meering of the Japanese Cancer Association
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Screening of microRNA as a prognosis factor for ovarian cancer.2016

    • Author(s)
      Fukagawa S., Miyata K., Kiyoshima C., Yotsumoto F., Yasunaga S. , Miyamoto S.
    • Organizer
      The 75th Annual Meering of the Japanese Cancer Association
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Screening of microRNA associated with HB-EGF as a biomarker of ovaryan prognosis.2016

    • Author(s)
      Kiyoshima C., Fukagawa S., Miyata K., Yotsumoto F., Yasunaga S. , Miyamoto S.
    • Organizer
      The 75th Annual Meering of the Japanese Cancer Association
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 飲酒関連遺伝子の一塩基多型を同時に検出する安価で迅速な duplex PCR-RFLP法の開発2016

    • Author(s)
      白須直人、安永晋一郎
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] A new strategy for manipulating expression and activity of Geminin could make it possible to regulate cell fates of HSCs.2016

    • Author(s)
      Takihara Y., Ohno Y., Suzuki-Takedachi K., Santo M., Yasunaga S., Ohtsubo M., Naka K.
    • Organizer
      ISEH (International Society for Experimental Hematology) 45th Annual Scientific Meeting
    • Place of Presentation
      San Diego, U.S.A.
    • 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, 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
  • [Presentation] DNA複製とクロマチンリモデリングを制御するCell-penetrating (CP-)Gemininの開発2015

    • Author(s)
      竹立(鈴木)恭子、大野芳典、黒木利知、安永晋一郎、山藤幹茂子、舛廣善和、花澤重正、大坪素秋、仲一仁、瀧原義宏
    • Organizer
      第38回日本分子生物学会・第88回日本生化学会合同年会(BMB2015)
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] A new strategy for manipulating expression and activety of Geminin, a cell-fate determinant for HSCs.2015

    • Author(s)
      Ohno Y., Suzuki-Takedachi K., Kurogi T., Santo M., Yasunaga S., Ohtsubo M., Naka K., Takihara Y.
    • Organizer
      The 77th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      Kanazawa, Japan.
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Analysis of molecular role for Geminin in self-renewal and differentiation of HSCs.2015

    • Author(s)
      Suzuki-Takedachi K.,Ohno Y., Kurogi T., Santo M., Yasunaga S., Ohtsubo M., Naka K., Takihara Y.
    • Organizer
      The 77th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      Kanazawa, Japan.
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Manipulation of the Geminin activety by using cell-penetrating Geminin and its domein-specific mutants.2015

    • Author(s)
      Ohno Y., Yasunaga S., Suzuki-Takedachi K., Kurogi T., Santo M., Ohtsubo M., Naka K., Takihara Y.
    • Organizer
      The 13th Stem Cell Research Symposium
    • Place of Presentation
      Tokyo, Japan.
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Cell-penetrating Geminin is exerted to provide a new strategy for manipulating the activity and number of HSCs.2015

    • Author(s)
      Kurogi T., Ohno Y., Yasunaga S., Suzuki-Takedachi K., Santo M., Ohtsubo M., Takihara Y.
    • Organizer
      The 5th International Symposium of RIRBM, Hiroshima University
    • Place of Presentation
      Hiroshima, Japan
    • Year and Date
      2015-03-02 – 2015-03-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Analysis of molecular rele for Geminin in self-renewal and differentiation of HSCs.2015

    • Author(s)
      Suzuki-Takedachi K., Yasunaga S., Ohno Y., Kurogi T., Santo M., Ohtsubo M., Takihara Y.
    • Organizer
      The 5th International Symposium of RIRBM, Hiroshima University
    • Place of Presentation
      Hiroshima, Japan
    • Year and Date
      2015-03-02 – 2015-03-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Simple diagnosis of STAT1 gain-of-function alleles in patient with chronic mucocutaneous candidiasis presenting various clinical signs.2015

    • Author(s)
      Mizoguchi Y., Okada S., Tsumura M., Yasunaga S., Takihara Y., Casanova J.-L., Morio T., Kobayashi M.
    • Organizer
      The 5th International Symposium of RIRBM, Hiroshima University
    • Place of Presentation
      Hiroshima, Japan
    • Year and Date
      2015-03-02 – 2015-03-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Effects of low-dose irradiation on the hematopoietic system.2015

    • Author(s)
      Yasunaga S., Ohno Y., Suzuki-Takedachi K., Kurogi T., Santo M., Ohtsubo M., Takihara Y.
    • Organizer
      The 5th International Symposium of RIRBM, Hiroshima University
    • Place of Presentation
      Hiroshima, Japan
    • Year and Date
      2015-03-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Geminin-EYFP knock-in mice provide a powerful tool for dissecting a molecular mechanism regulating self-renewal or differentiation of hematopoietic stem cells.2014

    • Author(s)
      Suzuki-Takedachi K., Yasunaga S., Ohno Y., Kurogi T., Ohtsubo M., Takihara Y.
    • Organizer
      The 37th Annual Meeting of the Molecular Biology of Japan
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Cell-penetrating recombinant Geminin protein may provide a new strategy for regulating self-renewal or cellular differentiation in hematopoietic stem cells.2014

    • Author(s)
      Kurogi T., Ohno Y., Yasunaga S., Suzuki-Takedachi K., Santo M., Masuhiro Y., Hanazawa S., Ohtsubo M., Takihara Y.
    • Organizer
      The 37th Annual Meeting of the Molecular Biology of Japan
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Geminin visualization aids detailed molecular analysis of self-renewing hematopoietic stem cells.2014

    • Author(s)
      Yasunaga S., Ohno Y., Suzuki-Takedachi K., Kurogi T., Santo M., Ohtsubo M., Takihara Y.
    • Organizer
      The 76th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Direct transmission of a cell-penetrating form of Geminin, a regulator for hematopoietic stem cells.2014

    • Author(s)
      Ohno Y., Yasunaga S., Kurogi T., Suzuki-Takedachi K., Santo M., Ohtsubo M., Takihara Y.
    • Organizer
      The 76th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Direct transduction of a cell-penetrating form of Geminin, a molecule regulating DNA replication and chromatin remodeling.2014

    • Author(s)
      Takihara Y., Yasunaga S., Ohno Y., Kurogi T., Suzuki-Takedachi K., , Santo M., Ohtsubo M.
    • Organizer
      ISEH (International Society for Experimental Hematology) 43rd Annual Scientific Meeting
    • Place of Presentation
      Montreal , Canada
    • Year and Date
      2014-08-21 – 2014-08-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification and functional analysis of self-renewing hematopoietic stem cells by using Geminin-EYFP knock-in mice.2014

    • Author(s)
      Yasunaga S., Ohno Y., Suzuki-Takedachi K., Kurogi T., , Santo M., Ohtsubo M., Takihara Y.
    • Organizer
      The 12th Stem Cell Research Symposium
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2014-05-30 – 2014-05-31
    • Related Report
      2014 Research-status Report
  • [Presentation] Geminin regulates transcription via chromatin remodeling to govern cellular proliferation and differentiation.2014

    • Author(s)
      Ohno Y., Yasunaga S., Kurogi T., Suzuki-Takedachi K., Santo M., Ohtsubo M., Takihara Y.
    • Organizer
      The 12th Stem Cell Research Symposium
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2014-05-30 – 2014-05-31
    • Related Report
      2014 Research-status Report
  • [Book] モデル・コア・カリキュラム対応 医用生化学-生体物質の代謝と異常-2017年版 ISBN978-4-9909426-0-12017

    • Author(s)
      安永晋一郎(編著)、黒木政秀、黒木求、瀬川波子、衣笠哲史、芝口浩智、白須直人、四元房典
    • Total Pages
      464
    • Publisher
      福岡大学医学部生化学講座
    • Related Report
      2016 Annual Research Report
  • [Book] モデル・コア・カリキュラム対応 医用生化学-生体物質の代謝と異常-2016年版2016

    • Author(s)
      安永晋一郎
    • Total Pages
      402
    • Publisher
      福岡大学医学部生化学講座 ISBN978-4-9903146-8-2
    • Related Report
      2015 Research-status Report
  • [Remarks] 福岡大学医学部生化学

    • URL

      http://www.med.fukuoka-u.ac.jp/biochem1/index-j.htm

    • Related Report
      2016 Annual Research Report
  • [Remarks] 福岡大学医学部生化学講座

    • URL

      http://www.med.fukuoka-u.ac.jp/biochem1/index-j.htm

    • Related Report
      2015 Research-status Report
  • [Remarks] 広島大学原爆放射線医科学研究所 幹細胞機能学研究分野

    • URL

      http://home.hiroshima-u.ac.jp/dscb/index.html

    • Related Report
      2015 Research-status Report
  • [Remarks] 広島大学 原爆放射線医科学研究所 幹細胞機能学研究分野

    • URL

      http://home.hiroshima-u.ac.jp/dscb/index.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 福岡大学 医学部 生化学講座

    • URL

      http://www.med.fukuoka-u.ac.jp/biochem1/index-j.htm

    • Related Report
      2014 Research-status Report

URL: 

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

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