QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

doi: 10.1242/10.1242/dev.00459

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Suzuki, A. Articles by Taniguchi, H. Search for Related Content PubMed PubMed Citation Articles by Suzuki, A. Articles by Taniguchi, H.

Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells

¹ Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
² Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
³ Department of Regenerative Medicine, Faculty of Medicine, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan

^* Author for correspondence (e-mail: rtanigu{at}med.yokohama-cu.ac.jp)

Accepted 26 February 2003

In liver development, a number of growth factors (GFs) and components of the extracellular matrix (ECMs) lead to differentiation of liver parenchymal cells. As the liver contains many cell types, specifically investigating their functional effects on hepatic stem cell populations is difficult. Prospective isolation and clonal assays for hepatic stem cells enable the examination of direct effects of GFs and ECMs on this rare cell fraction. Using previously purified cells that fulfill the criteria for hepatic stem cells, we examined how GFs and ECMs regulate differentiation in the developing liver. We show here that hepatocyte growth factor (HGF) induced early transition of albumin (ALB)-negative stem cells to ALB-positive hepatic precursors resembling hepatoblasts and then oncostatin M (OSM) promoted their differentiation to tryptophan-2, 3-dioxygenase (TO)-positive mature hepatocytes. During this transition, ECMs were necessary for the differentiation of stem cells and precursors, but their effects were only supportive. In the first step of stem cell differentiation induced by HGF, the expression of CCAAT/enhancer binding protein (C/EBP), a basic leucine zipper transcription factor, changed dramatically. When C/EBP function was inhibited in stem cells, they stopped differentiating to hepatocyte-lineage cells and proliferated actively. These are the first findings to illustrate the mechanism of hepatic stem cell differentiation in liver development.

Key words: Stem cell, Liver, Hepatocyte, C/EBP, Mouse

This article has been cited by other articles:

				N. Shiraki, K. Umeda, N. Sakashita, M. Takeya, K. Kume, and S. Kume Differentiation of mouse and human embryonic stem cells into hepatic lineages Genes Cells, July 1, 2008; 13(7): 731 - 746. [Abstract] [Full Text] [PDF]

				A. Suzuki, S. Sekiya, D. Buscher, J. C. Izpisua Belmonte, and H. Taniguchi Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression Development, May 1, 2008; 135(9): 1589 - 1595. [Abstract] [Full Text] [PDF]

				R. Miki, N. Tatsumi, K. Matsumoto, and Y. Yokouchi New primary culture systems to study the differentiation and proliferation of mouse fetal hepatoblasts Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G529 - G539. [Abstract] [Full Text] [PDF]

				M. Dodig, B. Ogunwale, S. Dasarathy, M. Li, B. Wang, and A. J. McCullough Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of {alpha}5beta1-integrin Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G154 - G164. [Abstract] [Full Text] [PDF]

				C. Duret, S. Gerbal-Chaloin, J. Ramos, J.-M. Fabre, E. Jacquet, F. Navarro, P. Blanc, A. Sa-Cunha, P. Maurel, and M. Daujat-Chavanieu Isolation, Characterization, and Differentiation to Hepatocyte-Like Cells of Nonparenchymal Epithelial Cells from Adult Human Liver Stem Cells, July 1, 2007; 25(7): 1779 - 1790. [Abstract] [Full Text] [PDF]

				S. S. Chen, W. Fitzgerald, J. Zimmerberg, H. K. Kleinman, and L. Margolis Cell-Cell and Cell-Extracellular Matrix Interactions Regulate Embryonic Stem Cell Differentiation Stem Cells, March 1, 2007; 25(3): 553 - 561. [Abstract] [Full Text] [PDF]

				N. Kamo, K. Yasuchika, H. Fujii, T. Hoppo, T. Machimoto, T. Ishii, N. Fujita, T. Tsuruo, J. K. Yamashita, H. Kubo, et al. Two populations of Thy1-positive mesenchymal cells regulate in vitro maturation of hepatic progenitor cells Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G526 - G534. [Abstract] [Full Text] [PDF]

				N. Tanimizu, H. Saito, K. Mostov, and A. Miyajima Long-term culture of hepatic progenitors derived from mouse Dlk+ hepatoblasts J. Cell Sci., December 15, 2004; 117(26): 6425 - 6434. [Abstract] [Full Text] [PDF]