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Regulation of Hemopoietic Stem Cells and Its Clinical Application

Research Project

Project/Area Number 06277103
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionOsaka University

Principal Investigator

KITAMURA Yukihiko  Osaka University, Medical School, Professor, 医学部, 教授 (70028520)

Co-Investigator(Kenkyū-buntansha) MIUA Yasusada  Jichi Medical School, Professor, 医学部, 教授 (60048965)
ATRAI Kenichi  The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (00012782)
SUDA Toshio  Kumamoto University, Medical School, Professor, 医学部, 教授 (60118453)
KANAKURA Yuzuru  Osaka University, Medical School, Professor, 医学部, 教授 (20177489)
浅野 茂隆  東京大学, 医科学研究所, 教授 (50134614)
井川 洋二  東京医科歯科大学, 医学部, 教授 (40085618)
高久 史麿 (高久 史磨)  自治医科大学, 医学部, 学長 (40048955)
Project Period (FY) 1994 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥101,900,000 (Direct Cost: ¥101,900,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥24,400,000 (Direct Cost: ¥24,400,000)
Fiscal Year 1996: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 1995: ¥22,500,000 (Direct Cost: ¥22,500,000)
Fiscal Year 1994: ¥28,000,000 (Direct Cost: ¥28,000,000)
KeywordsHemopoietic stem / Differentiation signal / Death signal / Hemoietic factor / Impact factor / Transcription factor / Kno-ck-out mouse / signal transduction / シグナル伝進 / 増殖因子 / 増殖因子受容体 / 骨髄移植 / Jak-Stat系 / 分化制御 / 受容体チロシンキナーゼ / ノックアウト・マウス / 増殖の制御 / 造血幹細胞の精製 / 造血因子 / チロシンキナーゼ / サイトカイン / 造血因子レセプター / 造血微小環境 / 造血支持細胞 / 造血幹細胞移植
Research Abstract

We carried out the research under three sub-projects ; 1) purfication and amplification of hemopoietic stem cells, 2) signals for settlement, proliferation, differentiation and death of hemopoietic stem cells, 3) factors for regulation of hemopoiesis. We finished the research with a great success. Fifty five participants became co-authors of very widely circulating journals (impact factor, over 20). One hundred and twenty nine paticipants became co-authors of widely circulating journals (impact factor, 20 to 10). One hundred and eighty three participants became co-authors of Blood (impact factor, 9.745). Two hundred and five participants became co-authors of moderately circulating journals other than Blood (impact factor, 5 to 10). The following results were obtaind. 1). A purified stem cell rescued a lethally irradiated mouse. 2). An experimental system by which embryonic stem cells effiently differentiate to blood cells was improved. 3). Studies of transcription factors that regulate … More development of blood cells were promoted. 4) Various knock-out mice were elabrated that lacked genes encoding transcription factors, hemopoietic factors, or hemopoietic factor receptors. 5). Pathways of signal transduction were clarified from various hemopoietic factor receptors. JAK-STAT systems are especially mportant for the signal transduction from hemopoietic factor receptors. 6). Knock-out mice of runt domain-gene family were elaborated. Liver hemopoiesis did not occur in a knock-out strain, and bone tissue did not develop in the other knock-out strain. 7). Gain-of-function mutations of c-kit gene were studied. Mast cell tumors resulted from one mutation, and gastrointestinal stromal tumors that may be derived from the interstitial cells of Cajal resulted from the other mutation. 8). Hemopoietic stem cells obtained from early mouse embryos responded to oncostatin M. 9). Evi-1 protein bound Smad3-Smad4 complex, and this inhibited the signal transduction from the TGFβ receptor. 10). Studies on the final stage of apoptosis were remarkably progressed. Less

Report

(6 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Hirota S,Kitamura Y et al: "Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors"Science. 279. 577-580 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kurokawa M,Hirai H et al: "The oncoprotein Evi-1 represses TGFβ signalling by inhibiting smad3"Nature. 394. 92-96 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishikawa SI et al: "In vitro generation of lymphohematopoietic cells from endothelial cells of murine embryos"Immunity. 8. 761-769 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Enari M,Nagata S et al: "Caspase-acticvated DNase that degrades DNA during apoptosis and its inhibitor ICAD"Nature. 391. 43-50 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mukoyama Y Miyajima A et al: "In vitro expansion of murine hematopoietic proqenitors derived the AGM region"Immunity. 8. 105-114 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ito A Kitamura Y et al: "Systematic method to odtain novel genes that are regulated by mi transcription factor(MITF)"Blood. 91. 3210-3221 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitamura Y et al: "Hematopoietic Lineages:Regulation of Cell Production and Development"marcel dikker,New York(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitamura Y et al: "Signal Transduction in Mast Cells and Basophils"Springer-Verlag,New York(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirota S.: "Gain-of-fanction of c-kit in human gastrointestinal stromal tumors"Science. 279. 577-580 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kurokawa M.: "The oncoprotein Evi-1 represses TGBβ signalling by inhibiting Smad3"Nature. 349. 92-96 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishikawa SI.: "In vitro generation of lymphohematoppoietic cells from endothelial cells of murine embryos"Immunity. 8. 761-769 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Enari M.: "Caspase-activated DNase that degrades DNA during apoptosis and its inhibitor ICAD"Nature. 391. 43-50 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mukoyama Y.: "In vitro expansion of murine hematopoietic progenitors derived the AGM region"Immunity. 8. 105-114 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ito A.: "Systematic method to obtain novel genes that are regulated bu mi transcription factor (MITF)"Blood. 91. 3210-3221 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitamura Y.: "Hematopoietic Lineages : Regulation of Cell Production and Development"marcel dikker, New York, (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitamura Y.: "Signal Transduction in Mast Cells and Basophils"Springer-Verlag, New York (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirota S,Kitamura Y et al: "Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors" Science. 279. 577-580 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kurokawa M,Hirai H et al: "The oncoprotein Evi-1 represses TGFβ signalling by inhibiting Smad3" Nature. 394. 92-96 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishikawa SI et al: "In vitro generation of lymphohematopoietic cells from endothelial cells of murine embryos" Immunity. 8. 761-769 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Enari M,Nagata S et al: "Caspase-activated DNase that degrades DNA during apoptosis and its inhibitor ICAD" Nature. 391. 43-50 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mukoyama Y Miyajima A et al: "In vitro expansion of murine hematopoietic pro-genitors derived the AGM region" Immunity. 8. 105-114 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ito A Kitamura Y et al: "Systematic method to obtain novel genes that are regulated by mi transcription factor (MITF)" Blood. 91. 3210-3221 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kitamura Y et al: "Hematopoietic Lineages: Regulation of Cell Production and Development (in press)" marcel dikker,New York,

    • Related Report
      1998 Annual Research Report
  • [Publications] Kitamura Y et al: "Signal Transduction in Mast Cells and Basophils (in press)" Springer-Verlag, New York,

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagata,S.: "Aptosis by death factor" Cell. 88. 355-365 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiroata,S.: "Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors" Scinece. 279. 577-580 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirao,A.: "Translocation of the Csk homologous kinase (Chk/Hyl) controls activity of CD36-ancored Lyn tyrosine kinase" EMBO Journal. 16. 2342-2351 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakamoto,O.: "Role of macrophage-stimulating protein and its receptor,RON tyrosine kinase,in ciliary motality" Journal of Clinical Investigation. 99. 701-709 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inada,T.: "Selective expression of the receptor tyrosine kinase,HTK,on human erythroid progenitor cells" Blood. 89. 2757-2765 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morii,E.: "Abnormal expression of mouse mast cell protease 5 gene in cultured mast cells derived from mi/mi mice" Blood. 90. 3057-3066 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Arai,K.: "Mechanism of signal transduction" Oxford press (in press),

    • Related Report
      1997 Annual Research Report
  • [Publications] Kitamura,Y.: "Signal transduction in mast cells and basophils" Landes Biosciences Publishers (in press),

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwama,A.: "STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via multifunctional site" EMBO Journal. 15. 5866-5875 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwamoto,N.: "Preferential hematopoiesis by paroxysmal nocturnal hemoglobinuria clone engrafted in SCID mice" Blood. 87. 4944-4948 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Muto,A.: "The β subunit of human granulocyte-macrophage colony stimulating factor receptor forms a homodimer" Journal of Experimental Medicine. 183. 1911-1916 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Itoh,T.: "Granulocyte-macrophage colony-stimulating factor provokes RAS activation and transcription of fos" Journal of Biological Chemistry. 271. 7587-7592 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morii,E.: "Regulation of mouse mast cell protease 6 gene expression by transcription factor encoded by mi locus" Blood. 88. 2488-2494 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsujimura,T.: "Involvement of transcription factor encoded by the mi locus in the expression of c-kit in cultured mast cells" Blood. 88. 1225-1233 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kitamura,Y: "Hematopoietic Lineages:Regulation of Cell Production and Development" marcel dekker(in press),

    • Related Report
      1996 Annual Research Report
  • [Publications] Kitamura,Y.: "Signal Transduction in Mast Cells and Basophils" R.G.Landes Biosciences Publishers(in press),

    • Related Report
      1996 Annual Research Report
  • [Publications] Morimoto,M.: "Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia" Blood. 86. 4323-4330 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takebayashi,K: "Recessive phenotype displayed by dominant negative MITF mutant is a result of impaired nuclear transfer" Molecular and Cellular Biology. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Sakamoto,O.: "Interleukin-13 selectively suppress the growth of human macrophage progenitors at the late stage" Blood. 85. 3487-3493 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Iwama,A.: "Terminal differentiation of murine residentperitoneal macrophages is characterized by expression of the STK" Blood. 86. 3394-3403 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Muto,A.: "The β subunit of human GM-CSF receptor forms a homodimer and is activated by association of subunit" Journal of Experimental Medicine. in press.

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishijima,I.: "A human GM-CSF receptor expressed in transgenic mice stimulates differentiation of all lineages" Molecular Biology of Cell. 6. 627-636 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kitamura,Y.: "Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function" Raven Press, New York, 270 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kitamura,Y.: "Hematopoietic Lineages: Regulation and Cell Production and Development" marcel dekker, New York (in press),

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamasaki,Masaru: "c-kit gene isexpressed by skin mast cells in embryos but not in puppies of Wsh/Wsh mice:age-dependent c-kit gene expression." Blood. 83. 3509-3516 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tsujimura,Tohru: "Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 by a point mutation." Blood. 83. 2619-2626 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kondo,Motonari: "Function participation of the IL-2 receptor gamma chain in IL-7 receptor complexes." Science. 263. 1453-1454 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamamura,Yasuko: "Activated Ki-Ras Complements erythropoietin signals in CTLL-2 cells,inducing tyrosine phosphorylation of a 160-KDa protein." Proceedings of National Academy of Sciences of United States of America. 91. 8866-8870 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kinoshita,Taisei: "Suppression of apoptotic death in hematopoietic cells by signalling through the IL-3/GM-CSF receptors." EMBO Journal. in press.

    • Related Report
      1994 Annual Research Report
  • [Publications] MUroi,Kazuo: "Expression of sialosy-Tn in solony forming unit-erythroid,erythroblasts,B cells,and a subset of CD4+ cells." Blood. 83. 84-91 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function" Raven Press(in press),

    • Related Report
      1994 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Immunobiology of Otorhinolaryngology" Kurger Publications, 674 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2019-02-15  

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