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Role for growth factors and extracellular matrixes in controlling hepatic stem cell differentiation

Research Project

Project/Area Number 12557096
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General surgery
Research InstitutionYokohama City University (2002)
University of Tsukuba (2000-2001)

Principal Investigator

TANIGUCHI Hideki  Yokohama City University, Department of Regenerative Medicine, Yokohama City University School of Medicine, 医学部, 教授 (70292555)

Co-Investigator(Kenkyū-buntansha) ETO Yuzuru  Yokohama City University, Pharmaceutical Research Laboratories, AJINOMOTO Co., 医薬研究所, 主任研究員
NAKAUCHI iromitsu  Yokohama City University, Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 医科学研究所, 教授 (40175485)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Keywordscell growth / differentiation / cytokines / 肝臓 / 再生 / 幹細胞 / 再生医学
Research Abstract

In the liver development, a number of growth factors (GFs) and extracellular matrixes (ECMs) lead to differentiation of the liver parenchymal cells. However, since the liver contains cells of many type, it is difficult to investigate their functional effects on hepatic stem cell population specifically. Prospective isolation and clonal assays for hepatic stem cells enable to examine direct effects of GFs and ECMs on such cell fraction. Using previously purified cells that fulfill the criteria for hepatic stem cells, we examined in this study how GFs and ECMs regulate their differentiation in the developing liver. We show here that HGF induced early transition of albumin (ALB)-negative stem cells to Alb-positive hepatic precursors regarding hepatoblasts, and then OSM promoted secondary their differentiation to finally tryptophan-2, 3-dioxygenase (TO)-positive mature hepatocytes. During such transition, ECMs are necessary for the differentiation of stem cells and precursors, but their effects are just supportive for them. In the first step of stem cell differentiation induced by HGF, the expression of CCAAT/enhancer birding protein (C/EBP), a basic leucine zipper protein of transcriptional factors, changed dramatically, and when the function of C/EBPs is inhibited in the stem cells, they stop turning to hepatocytes -lineage cells and proliferate actively. Those evidences are first findings to clear the mechanism of hepatic stem cell differentiation in the liver development.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] A.Suzuki, H.Taniguchi et al.: "Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells"Development. 130. 2513-2524 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Suzuki, H.Taniguchi et al.: "Establishment of clonal colony-forming assay system for pancreatic stem/progenitor cells"Cell Transplantation. 11(5). 451-453 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Miyashita, H.Taniguchi et al.: "Evidence for the hepatocyte differentiation from embryonic stem cells in vivo"Cell Transplantation. 11(5). 429-434 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Suzuki, H.Nakauchi, H.Taniguchi et al.: "Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver"The Journal of Cell Biology. 156(1). 173-184 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Suzuki, H.Taniguchi et al.: "Hepatic stem/progenitor cells with high-proliferative potential in liver organ-formation"Transplantation Proceedings. 10(4-5). 393-396 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 谷口 英樹(分担執筆): "再生医学(肝幹細胞の分離と臨床応用へのアプローチ)"中山書店. 6 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Susuki A, Iwama A, Miyahsita H, Nakauchi H, Taniguchi H: "Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells."Development. 130. 2513-2524 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki A, Oyama K, Fukao K, Nakauchi H, Tanigchi H: "Establishment of clonal colony-forming assay system for pancreatic stem/progenitor cells"Cell Transplantation. 11(5). 451-453 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyashita H, Suzuki A, Fukao K, Nakauchi H and Taniguchi H: "Evidence for the hepatocytes differentiation from embryonic stem cells in vitro."Cell Transplantation. 11(5). 429-434 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki A, Zhen Y. W., Kaneko S, Onodera M, Fukao K, Nakauchi H and Taniguchi H: "Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver."The Journal of Cell Biology. 156(1). 173-184 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A. Suzuki, Y. W. Zheng, K. Fukao, H. Nakauchi and H. Taniguchi: "Clonal expansion of hepatic stem/ progenitor cells following flow cytometric cell sorting."Cell Transplant. 10(4-5). 393-396 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A. Suzuki, Y. W. Zheng, K. Fukao, H. Nakauchi and H. Taniguchi: "Hepatic Stem/Progenitor Cells With High Proliferative Potential in Liver Organ Formation"Transplantation Proceedings. 33. 585-256 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Suzuki, H.Taniguchi, et al.: "Establishment of clonal colony-forming assay system for pancreatic stem/progenitor cells"Cell Transplantation. 11(5). 451-453 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Miyashita, H.Taniguchi et al.: "Evidence for the hepatocyte differentiation from embryonic stem cells in vivo"Cell Transplantation. 11(5). 429-434 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Hirasawa, H.Taniguchi, H.Nakauchi et al.: "Essential and Instructive Roles of GATA Factors in Eosinophil Development"J Exp Med. Jun.3;195(11). 1379-1386 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Suzuki, H.Nakauchi, H.Taniguchi et al.: "Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver"The Journal of Cell Biology. 156(1). 173-184 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 谷口 英樹: "肝臓幹細胞. 再生医療光学の最先端、 筏義人編集"シーエムシー出版. 7 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Suzuki, H.Taniguchi, et al.: "Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver"The Journal of Cell Biology. 156. 173-184 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Suzuki, H.Taniguchi, et al.: "Clonal expansion of hepatic stem/progenitor cells following flow cytometric cell sorting"Cell Transplant 10. 10. 393-396 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Suzuki, H.Taniguchi, et al.: "Hepatic stem/progenitor cells with high-proliferative potential in liver organ-formation"Transplan Proc33. 33. 585-586 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Suzuki,H.Taniguchi et al: "Flowcytometric separation and enrichment of multipotent hepatic progenitor cells in mouse developing liver"Hepatology. 32. 1230-1239 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Taniguchi et al: "Usefulness of flowcytometric cell sorting for enrichment of hepatic stem cells in the liver"Transplantation Proceedings. 32. 249-251 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Taniguchi et al: "Clonogenic colony forming ability of flowcytometrically isolated hepatic stem/progenitor cells in the murine fetal liver"Cell Transplantation. 9. 697-700 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 谷口英樹,鈴木淳史: "多能性肝幹細胞の分化・増殖機構の解明"蛋白・核酸・酵素. 45. 256-262 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 谷口英樹,鈴木淳史: "「臓器置換」から「臓器再生」へ"細胞工学. 19. 869-873 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 谷口英樹: "肝臓における再生医療の展開"今日の移植. 13. 228-232 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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