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Molecular mechanisms for regulation of hematopoietic and leukemia stem cell population by nucleolar molecules

Research Project

Project/Area Number 18390281
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKanazawa University

Principal Investigator

HIRAO Atsushi  Kanazawa University, がん研究所, 教授 (90343350)

Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,340,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywords造血幹細胞 / 白血病 / 分化 / 核小体 / 細胞分化
Research Abstract

正常造血幹細胞と白血病幹細胞の共通性を解明するアプローチとして、核小体に焦点を当てて研究を進めた。核小体分子Nucleosteminは、未分化な造血幹細胞に高い発現が認められた。Nucleosteminの発現をGFPによってモニターするレポーターシステムを構築し、造血系で解析したところ、正常造血および骨髄性白血病において、未分化細胞を濃縮することができた。これらの知見は、将来の白血病治療薬の標的となる分子の特定に寄与することが期待された。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (60 results)

All 2009 2008 2007 2006

All Journal Article (26 results) (of which Peer Reviewed: 19 results) Presentation (34 results)

  • [Journal Article] Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity2008

    • Author(s)
      Ohmura M, Naka K, Hoshii T, Muraguchi T, Shugo H, Tamase A, Uema N, Ooshio T, Arai F, Takubo K, Nagamatsu G, Hamaguchi I, Takagi M, Ishihara M, Sakurada K, Miyaji H, Suda T, Hirao A.
    • Journal Title

      Stem Cells 12

      Pages: 3237-46

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stem cell defects in ATM-deficient undifferentiated spermatogonia through DNA damage-induced cell cycle arrest2008

    • Author(s)
      Takubo K, Ohmura M, Azuma M, Nagamatsu G, Yamada W, Arai F, Hirao A, Suda T.
    • Journal Title

      Cell Stem Cell 2

      Pages: 170-182

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells2008

    • Author(s)
      Oguma K, Oshima H, Aoki M, Uchio R, Naka K, Nakamura S, Hirao A, Saya H, Taketo MM, Oshima M.
    • Journal Title

      EMBO J. 27

      Pages: 1671-81

    • NAID

      120001670272

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of reactive oxygen species and genomic stability in hematopoietic stem cells2008

    • Author(s)
      Naka K, Muraguchi T, Hoshii T, Hirao A.
    • Journal Title

      Antioxid Redox Signal 10

      Pages: 1883-94

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity.2008

    • Author(s)
      Ohmura M, et. al. (著者18名中18番)
    • Journal Title

      Stem Cells. 39

      Pages: 3237-46

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of reactive oxygen species and genomic stability in hematopoietic stem cells.2008

    • Author(s)
      Naka K (著者4名中4番)
    • Journal Title

      Antioxid Redox Signal. 11

      Pages: 1883-94

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells.2008

    • Author(s)
      Oguma K, et al (著者1O名中7番)
    • Journal Title

      EMBO J. 27

      Pages: 1671-81

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stem cell defects in ATM-deficient undifferentiated spermatogonia through DNA damage-induced cell cycle arrest2008

    • Author(s)
      Keiyo Takubo, 他
    • Journal Title

      Cell Stem Cell 2

      Pages: 170-182

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular bases for self-renewal and differentiation of leukemic stem cells2008

    • Author(s)
      Kazuhito Naka, 他
    • Journal Title

      Curr. Cancer Therapy (掲載確定印刷中)

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Foxo3a is essential for maintenance of the hematopoietic stem cell pool2007

    • Author(s)
      Miyamoto K, Araki YK, Naka K, Arai F, Takubo K, Yamazaki S, Matsuoka S, Miyamoto T, Ito K, Ohmura M, Chen C, Hosokawa K, Nakauchi H, Nakayama K, Nakayama KI, Harada M, Motoyama N, Suda T, Hirao A.
    • Journal Title

      Cell Stem Cell 1

      Pages: 101-112

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals2007

    • Author(s)
      Ohtani N, Imamura Y, Yamakoshi K, Hirota F, Nakayama R, Kubo Y, Ishimaru N, Takahashi A, Hirao A, Shimizu T, Mann DJ, Saya H, Hayashi Y, Arase S, Matsumoto M, Kazuki N, Hara E.
    • Journal Title

      Proc Natl Acad Sci USA 104

      Pages: 15034-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of reactive oxygen species by atm is essential for proper response to DNA double-strand breaks in lymphocytes2007

    • Author(s)
      Ito K, Takubo K, Arai F, Satoh H, Matsuoka S, Ohmura M, Naka K, Azuma M, Miyamoto K, Hosokawa K, Ikeda Y, Mak TW, Suda T, Hirao A.
    • Journal Title

      J Immunol 178

      Pages: 103-10

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cross-talk between Chk1 and Chk2 in double-mutant thymocytes2007

    • Author(s)
      Zaugg K, Su YW, Reilly PT, Moolani Y, Cheung CC, Hakem R, Hirao A, Liu Q, Elledge SJ, Mak TW.
    • Journal Title

      Proc Natl Acad Sci U S A 104

      Pages: 3805-10

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death2007

    • Author(s)
      Iwanaga A, Sato T, Sugihara K, Hirao A, Takakura N, Okamoto H, Asano M, Yoshioka K.
    • Journal Title

      Neurosci Lett 429

      Pages: 43-8

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the self-renewal ability of tissue stem cells by tumor-related genes2007

    • Author(s)
      Naka K, Ohmura M, Hirao A.
    • Journal Title

      Cancer Biomark 3

      Pages: 193-201

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Foxo3a is essential for maintenance of the hematopoietic stem cell pool2007

    • Author(s)
      Kana Miyamoto, 他
    • Journal Title

      Cell Stem Cell 1

      Pages: 101-112

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals2007

    • Author(s)
      Naoko Ohtani, 他
    • Journal Title

      Proc Natl Acad Sci U S A 104

      Pages: 15034-9

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death2007

    • Author(s)
      Asuka Iwanaga
    • Journal Title

      Neurosci Lett 429

      Pages: 43-8

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the self-renewal ability of tissue stem cells by tumor-related genes2007

    • Author(s)
      Kazuhito Naka, 他
    • Journal Title

      Cancer Biomarkers 3

      Pages: 193-201

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Regulation of reactive oxygen species by atm is essential for proper response to DNA double-strand breaks in lymphocytes.2007

    • Author(s)
      Ito K., et al.Hirao A(計14名中14番)
    • Journal Title

      J Immunol. 178

      Pages: 103-10

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cross-talk between Chk1 and Chk2 in double-mutant thymocytes.2007

    • Author(s)
      Zaugg K., et al.Hirao A(計9名中7番)
    • Journal Title

      Proc Natl Acad Sci U S A. 104

      Pages: 3805-10

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Foxo3a Is Essential for Maintenance of the Hematopoietic Stem Cell Pool.2007

    • Author(s)
      Miyamoto K.et al.Hirao A(計18名中18番)
    • Journal Title

      Cell Stem Cell 1(印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells2006

    • Author(s)
      Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T.
    • Journal Title

      Nature Med. 12

      Pages: 446-451

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Premeiotic germ cell defect in seminiferous tubules of Atm-null testis2006

    • Author(s)
      Takubo K, Hirao A, Ohmura M, Azuma M, Arai F, Nagamatsu G, Suda T.
    • Journal Title

      Biochem Biophys Res Commun 351

      Pages: 993-8

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells.2006

    • Author(s)
      Ito K., et al.Hirao A(計11名中2番)
    • Journal Title

      Nature Med. 12

      Pages: 446-451

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Premeiotic germ cell defect in seminiferous tubules of Atm-null testis.2006

    • Author(s)
      Ito K., et al.Hirao A(計7名中2番)
    • Journal Title

      Biochem Biophys Res Commun. 351

      Pages: 993-8

    • Related Report
      2006 Annual Research Report
  • [Presentation] Roles of forkhead transcription factor Fox03a in normal hematopoiesis and leukemia.2009

    • Author(s)
      Hirao A
    • Organizer
      USA-Japan Cooperative Cancer Workshop 2009
    • Place of Presentation
      米国ハワイ
    • Year and Date
      2009-03-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] Effects of aging-or senescence-related factors on stem cell function and tissue homeostasis in vivo2008

    • Author(s)
      Hirao A.
    • Organizer
      BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of aging- or senescence-related factors on stem cell function and tissue homeostasis in vivo.2008

    • Author(s)
      Hirao A
    • Organizer
      BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 正常および腫瘍組織における幹細胞システム2008

    • Author(s)
      平尾敦
    • Organizer
      第45回日本婦人科腫瘍学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2008-11-22
    • Related Report
      2008 Final Research Report
  • [Presentation] Stemness in normal and malignant tissues2008

    • Author(s)
      Hirao A
    • Organizer
      第67回日本癌学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-27
    • Related Report
      2008 Final Research Report
  • [Presentation] Nucleosteminプロモーター活性による白血病幹細胞の同定2008

    • Author(s)
      仲一仁, 大村昌子, 石原正彦、宮地宏昌、須田年生、平尾敦
    • Organizer
      第67回日本癌学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-27
    • Related Report
      2008 Final Research Report
  • [Presentation] Sternness in normal and malignant tissues.2008

    • Author(s)
      Hirao A
    • Organizer
      第67回日本癌学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] 36th Congress of2008

    • Author(s)
      HIrao A, Stemness in normal, malignant tissues
    • Organizer
      the International Society of Oncology & BioMarkers
    • Place of Presentation
      Tokyo
    • Year and Date
      2008-10-07
    • Related Report
      2008 Final Research Report
  • [Presentation] Sternness in normal and malignant tissues.2008

    • Author(s)
      Hirao A
    • Organizer
      Mechanisms of Early Differentiation, Summer School
    • Place of Presentation
      ドイツ
    • Year and Date
      2008-09-03
    • Related Report
      2008 Annual Research Report
  • [Presentation] Stemness in normal and malignant tissues2008

    • Author(s)
      Hirao A.
    • Organizer
      The third International workshop on Cell Regulations in Division and Arrest
    • Place of Presentation
      Okinawa
    • Year and Date
      2008-04-09
    • Related Report
      2008 Final Research Report
  • [Presentation] Nucleostemin-GFPレポーターシステムによる白血病幹細胞の同定2008

    • Author(s)
      仲一仁, 大村昌子, 村口輝行, 星居孝之, 須田年生, 平尾敦
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] Mechanisms of Early Differentiation2008

    • Author(s)
      Hirao A, Stemness in normal, malignant tissues
    • Organizer
      Summer School
    • Place of Presentation
      Barsinghausen, Germany
    • Related Report
      2008 Final Research Report
  • [Presentation] Prospective identification of leukemic stem cells by promoter activity of nucleostemin gene2008

    • Author(s)
      Naka K, Ohmura M, Muraguchi T, Hoshii T, Hirao A.
    • Organizer
      6^<th> International Society of Stem Cell Research
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Nucleostemin-GFPレポーターシステムによる白血病幹細胞の同定2008

    • Author(s)
      仲一仁, 大村昌子, 村口輝行, 星居孝之, 平尾敦
    • Organizer
      第6回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] Identification of tumor-initiating cells by using Nucleostemin promoter activity2008

    • Author(s)
      Naka K, Ohmura M, Muraguchi T, Hoshii T, Hirao A.
    • Organizer
      Keystone Symposia, Tumor suppressor and stem cell biology
    • Place of Presentation
      Vancouver
    • Related Report
      2008 Final Research Report
  • [Presentation] 幹細胞制御における組織間共通性2007

    • Author(s)
      平尾敦
    • Organizer
      第10回日本組織工学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-08
    • Related Report
      2008 Final Research Report
  • [Presentation] 造血幹細胞の自己複製と老化2007

    • Author(s)
      平尾敦
    • Organizer
      第69回日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-07
    • Related Report
      2008 Final Research Report
  • [Presentation] Stemness genes in cancer2007

    • Author(s)
      平尾敦
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Related Report
      2008 Final Research Report
  • [Presentation] NucleosteminプロモーターGFPトランスジェニックマウスによる造血幹細胞標識システムの樹立2007

    • Author(s)
      仲 一仁, 他
    • Organizer
      第66回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] Establishment of a labeling system for hematopoietic stem cells by nucleostemin-enhancer/promoter driving GFP transgenic mice2007

    • Author(s)
      Kazuhito Naka, 他
    • Organizer
      The 5th International Society of Stem Cell Research
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      2007-06-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] Nucleosteminの発現による組織幹細胞の可視化と同定2007

    • Author(s)
      大村 昌子, 他
    • Organizer
      幹細胞シンポジウム
    • Place of Presentation
      兵庫
    • Year and Date
      2007-05-18
    • Related Report
      2007 Annual Research Report
  • [Presentation] The 49^<th> American Society2007

    • Author(s)
      Naka K, Ohmura M, Suda T, Hirao A
    • Organizer
      of Hematology Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] NucleosteminプロモーターGFP トランスジェニックマウスによる造血幹細胞標識システムの樹立2007

    • Author(s)
      仲一仁, 大村昌子, 野口亜希, 石原正彦、宮地宏昌、須田年生, 平尾敦
    • Organizer
      第66回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] The 5^<th> International Society2007

    • Author(s)
      Naka K, Ohmura M, Arai F, Suda T, Hirao A.
    • Organizer
      of Stem Cell Research
    • Place of Presentation
      Cairns,Australia
    • Related Report
      2008 Final Research Report
  • [Presentation] Nucleosteminの発現による組織幹細胞の可視化と同定2007

    • Author(s)
      大村昌子、仲一仁、木下雅史、玉瀬玲、新井文用、永松剛、田久保圭誉、照田展大、須田年生、平尾敦
    • Organizer
      第5回幹細胞シンポジウム
    • Place of Presentation
      淡路島
    • Related Report
      2008 Final Research Report
  • [Presentation] Regulation of stem cell self-renewal by aging related genes2007

    • Author(s)
      Hirao A
    • Organizer
      The second International workshop on Cell Regulations in Division and Arrest
    • Place of Presentation
      Okinawa
    • Related Report
      2008 Final Research Report
  • [Presentation] Establishment of a Labeling System for Hematopoietic Stem Cells by Nucleostemin Enhancer/Promoter-GFP Transgenic Mice2007

    • Author(s)
      Kazuhito Naka, 他
    • Organizer
      The 49th American Society of Hematology Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Regulation of stem cell self-renewal by tumor related genes2006

    • Author(s)
      Hirao A
    • Organizer
      Sixteenth International Symposium of the Hiroshima Cancer Seminar
    • Place of Presentation
      Hiroshima
    • Year and Date
      2006-10-22
    • Related Report
      2008 Final Research Report
  • [Presentation] 組織幹細胞マーキング法の開発2006

    • Author(s)
      大村昌子、仲一仁、新井文用、木下雅史、玉瀬玲、松岡佐保子、伊藤圭介、宮本佳奈、田久保圭誉、須田年生、平尾敦
    • Organizer
      第68回日本血液学会
    • Place of Presentation
      福岡
    • Year and Date
      2006-10-08
    • Related Report
      2008 Final Research Report
  • [Presentation] Regulation of stem cell self-renewal by aging-related genes2006

    • Author(s)
      Hirao A
    • Organizer
      35^<th> Annual Scientific Meeting International Society for Experimental Hematology
    • Place of Presentation
      Minneapolis, USA
    • Year and Date
      2006-09-26
    • Related Report
      2008 Final Research Report
  • [Presentation] ROS regulation and self-renewal capacity2006

    • Author(s)
      Hirao A
    • Organizer
      International Symposium on Gas Biology : Hematopoietic stem cells
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-06-27
    • Related Report
      2008 Final Research Report
  • [Presentation] 幹細胞自己複製制御と老化・寿命制御の共通性2006

    • Author(s)
      平尾敦
    • Organizer
      老年医学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2006-06-08
    • Related Report
      2008 Final Research Report
  • [Presentation] 核小体分子Nucleosteminによる生殖幹細胞制御機構2006

    • Author(s)
      大村昌子、新井文用、仲一仁、田久保圭誉、東真樹、須田年生、平尾敦
    • Organizer
      第4回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2006-05-20
    • Related Report
      2008 Final Research Report
  • [Presentation] The 19^<th> Naito Conference2006

    • Author(s)
      Hirao A
    • Organizer
      Molecular Basis for Maintenance and Differentiation of Stem Cells[II]Nov
    • Place of Presentation
      Kanagawa
    • Year and Date
      2006-01-05
    • Related Report
      2008 Final Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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