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1998 Fiscal Year Final Research Report Summary

Analysis of crosstalks between hematopoietic signals and their molecular mechanisms

Research Project

Project/Area Number 09470232
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

SONODA Yoshiaki  Department of Medicine, Kyoto Prefectural University of Medicine, Associate Professor, 医学部, 助教授 (60206688)

Co-Investigator(Kenkyū-buntansha) KIMURA Takafumi  Department of Medicine, Kyoto Prefectural University of Medicine, Assistant, 医学部, 助手 (30275193)
OKUDA Tsukasa  Department of Medicine, Kyoto Prefectural University of Medicine, Assistant Prof, 医学部, 講師 (30291587)
MURAKAMI Akira  Department of Polymer Science, Kyoto Institute of Technology, Professor, 繊維学部, 教授 (60210001)
Project Period (FY) 1997 – 1998
Keywordshematopoietic signal / crosstalk / hematopoietic stem cell / gp130 / IL-6 / c-kit / IL-3 / transcription factor
Research Abstract

Multicolor analysis of the expression of cell surface differentiation antigens, cytokine receptors, and gpl3O on BM, PBSC, and CB-derived CD34^+ cells revealed that the expression patterns differ between different stem/progenitor sources. First of all, we assessed the biologic role of signaling through gp13O, a signal-transducing receptor (R) component, in human hematopoiesis in vitro. Although PBSC-derived CD34^+ cells ubiquitously expressed gpl3O and IL-3Ralpha, IL-6Ralpha was only detected on 80% of these CD34^+ cells. We sorted CD34^+IL-6R^- cells and studied the effect on hematopoietic colony formation of signaling through gpl3O activated by a combination of IL-6 and recombinant soluble IL-6R (sIL-6R) in the presence of SCF and IL-3. Signals activated by SCF, IL-6/sIL-6R complex alone did not induce significant colony formation. However, a combination of IL-3, SCF, and IL-6/sIL-6R complex dramatically induced many neutrophil (CFU-G), erythroid-burst (BFU-E), mixed (CFU-Mix), and m … More egakaryocyte (CFU-Meg) colony formations. Our data suggested that LL-3 support was important forsurvival and initial proliferation, whereas SCF was important for enhancement of the proliferation of progenitors. The signal through gpl3O activated by IL-6/sIL-6R complex may mainly contribute to the maturation of progenitors in the presence of IL-3 and SCF.These results suggest that simultaneous activation of the three signals through gpl3O, c-kit, and IL-3R can induce in vitro proliferation and differentiation of trilineage hematopoietic progenitors in the absence of terminally acting lineage-specific factors.
Next, we tried to study molecular mechanisms of the crosstalks between these three signals. First, we established the method that allowed a great expansion of CFU-E in vitro. We obtained cell lysates from expanded CFU-Es, and analysed the tyrosine phosphorylation pattern after the stimulation of three signals or Epo. Simultaneously, we analysed the activation pattern of JAK-STAT pathway and MAPK pathway using immunoprecipitation and immunoblotting, and gel shift assay. Data accumulated suggest that activation of three signals may lead to cross-activation of additional signals. These molecular biologic analysis of signal transduction may provide a better understanding of interactions among signals through gpl3O and specific cytokine receptors and/or receptor type tyrosine kinases. Less

  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Sakabe H et al.: "Functional differences between subpopulations of mobilized peripheral blood-derived CD34+ cells---" Stem Cells. 15. 73-81 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda Y et al.: "Characterization of peripheral blood stem cells." Jpn J Apheresis. 16(1). 44-49 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohmizono. Y et al.: "Thrombopoietin auguments ex vivo expansion of human cord blood-derived hematopoietic progenitors ----" Leukemia. 11. 524-530 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda Y et al.: "Human flt3 ligand acts on myeloid as well as multipotential progenitors derived from purified ---" Eur J Haematol. 58. 257-264 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanimukai S et al.: "Recombinant human c-Mpl ligand (thrombopoietin) ---" Exp Hematol. 25. 1025-1033 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda Y et al.: "Action of human interleukin-4 and stem cell factor on erythroid and mixed colony formation by peripheral ---" Br J Haematol. 96. 781-789 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura T et al: "Simultaneous activation of signals through gp130,c-kit,and interleukin-3 receptor promotes---" Blood. 90. 4767-4778 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue K et al.: "Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia." Blood. 89. 1405-1412 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田 精昭: "末梢血幹細胞移植の紹介" 外科. 59. 719-723 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田 精昭: "末梢血幹細胞移植の実際 -基礎編-" 外科. 59. 853-859 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田 精昭: "末梢血幹細胞移植の実際 -臨床編-" 外科. 59. 981-988 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田 精昭: "造血幹細胞移植の未来" 外科. 59. 1088-1094 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakabe H et al.: "Human cord blood-derived primitive progenitors are enriched in CD34+c-kit- cells ---" Leukemia. 12. 728-734 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakabe H et al.: "Haematopoietic action of flt3 ligand on cord blood-derived CD34-positive cells expressing different --" Eur J Haematol. 60. 297-306 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwai T et al.: "Frequent aberration of FHIT gene expression in ---" Cancer Research. 58. 5182-5187 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田 精昭: "末梢血幹細胞移植の基礎 - 末梢血幹細胞の特徴" 産婦人科の実際. 47. 3-11 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中川 修一 他: "精巣腫瘍における自家末梢血幹細胞移植の現状と課題" 自己血輸血. 11. 9-14 (1998)

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      「研究成果報告書概要(和文)」より
  • [Publications] 中川 修一 他: "精巣腫瘍に対する自家末梢血幹細胞移植の現況と将来" Biotherapy. 12. 483-488 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中川 修一 他: "進行性精巣腫瘍に対するPBSCT併用超大量化学療法" 癌治療と宿主. 10. 70-77 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田 精昭 他: "造血幹細胞の特徴" 日本輸血学会雑誌. 44. 508-513 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 藤井 浩 他: "Double PBSCTにより寛解が得られた初回寛解導入不成功の悪性リンパ腫" 臨床血液. 39. 369-373 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 兼子 裕人 他: "固形腫瘍患者における Isolex 300 を用いたCD34陽性細胞の分離と自己末梢血幹細胞移植への応用" 臨床血液. 39. 652-657 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田 精昭: "専門医を目指すケース・メソッド・アプローチ" 阿部達生、横田昇平編、日本医事新報社, 208 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田 精昭: "新しい造血幹細胞移植" 原田実根、加藤俊一、薗田精昭編、南江堂, 212 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakabe H, Ohmizono Y, Tanimukai S, Kimura T, Mori KJ, Abe T, Sonoda Y: "Functional differences between subpopulations of mobilized peripheral blood-derived CD34^+ cells expressing different levels of HLA-DR, CD33, CD38, and c-kit antigens." Stem Cells. 15. 73-81 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda Y, Sakabe H, Kimura T, Tanimukai S, Ohmizono Y, Mori KJ, Abe T: "Characterization of peripheral blood stem cells." Jpn J Apheresis. 16. 44-49 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohmizono Y, Sakabe H, Kimura T, Tanimukai S, Matsumura T, Miyazaki H, Lyman SD, Sonoda Y: "Thrombopoietin auguments ex vivo expansion of human cord blood-derived hematopoietic progenitors in combination with stem cell factor and flt3 ligand." Leukemia. 11. 524-530 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda Y, Kimura T, Sakabe H, Tanimukai S, Ohmizono Y, Nakagawa S, Yokota S, Lyman SD, Abe T: "Human flt3 ligand acts on myeloid as well as multipotential progenitors derived from purified CD34^+ blood progenitors expressing different levels of c-kit protein." Eur J Haemato. 58. 257-264 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanimukai S, Kimura T, Sakabe H, Ohmizono Y, Kato T, Miyazaki H, Yamagishi H, Sonoda Y: "Recombinant human c-Mpl ligand (thrombopoietin) not only acts on megakaryocyte progenitors, but also on erythroid and multipotential progenitors in vitro." Exp Hematol. 25. 1025-1033 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda Y, Kimura T, Ohmizono Y, Sakabe H, Tanimukai S, Yokota S, Clark SC, Abe T: "Action of human interleukin-4 and stem cell factor on erythroid and mixed colony formation by peripheral blood-derived CD34^+ c-kit^<high> or CD34^+ c-kit^<low> cells." Br J Haematol. 96. 781-789 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue K, Ogawa H, Sonoda Y, Kimura T, Sakabe H, Oka Y, Miyake S, Tamaki H, Oji Y, Yamagami T, Tatekawa T, Soma T, Kishimoto T, Sugiyama H: "Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia" Blood. 89. 1405-1412 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura T, Sakabe H, Tanimukai S, Abe T, Urata Y, Yasukawa K, Okano A, Taga T, Sugiyama H, Kishimoto T, Sonoda Y: "Simultaneous activation of signals through gp130, c-kit, and interleukin-3 receptor promotes a trilineage blood cell production in the absence of terminally acting lineage-specific factors" Blood. 90. 4767-4778 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakabe H, Yahata N, Kimura T, Zeng ZZ, Minamiguchi H, Kaneko H, Mori KJ, Ohyashiki K, Ohyashiki JH, Toyama K, Abe T, Sonoda Y: "Human cord blood-derived primitive progenitors are enriched in CD34^+ c-kit^- cells : correlation between long-term culture-initiating cells and telomerase expression" Leukemia. 12. 728-734 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakabe H, Kimura T, Zeng ZZ, Minamiguchi H, Tsuda S, Yokota S, Hodohara K, Abe T, Lyman SD, Sonoda Y: "Haematopoietic action of flt3 ligand on cord blood-derived CD34-positive cells expressing different levels of flt3 or c-kit tyrosine kinase receptor : comparison with stem cell factor" Eur J Haematol. 60. 297-306 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwai T, Yokota S, Nakao M, Nakazawa N, Taniwaki M, Kimura T, Sonoda Y, Kaneko H, Okuda T, Azuma H, Oka T, Takeda T, Watanabe A, Kikuta A, Asami K, Sekine I, Matsushita T, Tsuchiya T, Mimaya J, Koizumi S, Ohta S, Miyake M, Takaue Y, Iwai A, Nishikawa K, Matsumoto K, Kawakami K, Hakura N, Fujimoto T: "Frequent aberration of FHIT gene expression in acute leukemia" Cancer Research. 58. 5182-5187 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaneko H, Kimura T, Tsuda S, Ohkawara Y, Abe T, Sonoda Y: "CE34-positive cell selection using an Isolex 300 system in patients with solid tumors and its application for autologous peripheral blood stem cell transplantation" Jpn J Hematol. 39. 652-657 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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