Document Detail

New primary culture systems to study the differentiation and proliferation of mouse fetal hepatoblasts.
MedLine Citation:
PMID:  18096607     Owner:  NLM     Status:  MEDLINE    
Hepatoblasts have the potential to differentiate into both hepatocytes and biliary epithelial cells through a differentiation program that has not been fully elucidated. With the aim to better define the mechanism of differentiation of hepatoblasts, we isolated hepatoblasts and established new culture systems. We isolated hepatoblasts from E12.5 fetal mouse liver by using E-cadherin. The E-cadherin+ cells expressed alpha-fetoprotein (AFP) and albumin (Alb) but not cytokeratin 19 (CK19). Transplantation of the E-cadherin+ cells into mice that had been subjected to liver injury or biliary epithelial injury led to differentiation of the cells into hepatocytes or biliary epithelial cells, respectively. In a low-cell-density culture system in the absence of additional growth factors, E-cadherin+ cells formed colonies of various sizes, largely comprising Alb-positive cells. Supplementation of the culture medium with hepatocyte growth factor and epidermal growth factor promoted proliferation of the cells. Thus the low-cell-density culture system should be useful to identify inductive factors that regulate the proliferation and differentiation of hepatoblasts. In a high-cell-density system in the presence of oncostatin M+dexamethasone, E14.5, but not E12.5, E-cadherin+ cells differentiated into mature hepatocytes, suggesting that unidentified factors are involved in hepatic maturation. Culture of E-cadherin+ cells derived from E12.5 or E14.5 liver under high-cell-density conditions should allow elucidation of the mechanism of hepatic differentiation in greater detail. These new culture systems should be of use to identify growth factors that induce hepatoblasts to proliferate or differentiate into hepatocytes and biliary epithelial cells.
Rika Miki; Norifumi Tatsumi; Ken Matsumoto; Yuji Yokouchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-20
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  294     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-13     Completed Date:  2008-03-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G529-39     Citation Subset:  IM    
Division of Pattern Formation, Department of Organogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan.
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MeSH Terms
Bile Ducts / cytology
Cadherins / metabolism
Cell Differentiation / physiology
Cell Proliferation
Cell Separation
Cell Size
Cell Transplantation
Cells, Cultured
Epidermal Growth Factor / physiology
Hepatocyte Growth Factor / physiology
Hepatocytes / physiology*
Liver / cytology*,  embryology*
Mice, Inbred ICR
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/Cadherins; 62229-50-9/Epidermal Growth Factor; 67256-21-7/Hepatocyte Growth Factor

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