2002 Fiscal Year Final Research Report Summary
Role for growth factors and extracellular matrixes in controlling hepatic stem cell differentiation
| Project/Area Number |
12557096
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General surgery
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| Research Institution | Yokohama City University (2002)
University of Tsukuba (2000-2001) |
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Principal Investigator |
TANIGUCHI Hideki Yokohama City University, Department of Regenerative Medicine, Yokohama City University School of Medicine, 医学部, 教授 (70292555)
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| 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)
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| Project Period (FY) |
2000 – 2002
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| Keywords | cell growth / differentiation / cytokines |
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| 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.
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