Document Detail


Quantitative gene expression profiling reveals a fetal hepatic phenotype of murine ES-derived hepatocytes.
MedLine Citation:
PMID:  15005571     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To use embryonic stem (ES) cells in future therapeutical applications, differentiated hepatic phenotypes with specific liver functions would be necessary. We analyzed albumin (ALB), alpha-fetoprotein (AFP) and hepatic transcription factor (TF) gene expression in tissues derived from embryonic, fetal and adult liver, and compared the gene expression profiles with those from mouse ES cells after hepatic differentiation and from cultured adult hepatocytes. The mRNA expression of hepatocyte nuclear factor (HNF)-1alpha,beta, -3alpha,beta, -4alpha, -6, CCAAT/enhancer binding protein (C/EBP) alpha,beta, ALB and AFP relative to glyceralaldehyde-3-phosphate dehydrogenase (GAPDH) were studied by "real time" RT-PCR. ALBand AFP-expression was also determined by in situ hybridization (tissue) and immunofluorescence (ES-derived cells after hepatic differentiation, ES-HPC). Peak levels for HNF-1alpha, -3alpha, -4alpha and -6 were detected in early liver development at d9.5 and d11.5. C/EBPalpha and beta were most abundantly expressed in adult liver. ALB mRNA increased steadily from d10.5 on and was maximally present in adult liver. AFP was present at d9.5, peaked at d15.5 and dramatically declined in mature liver tissue. Based on immunofluorescence, ALB and AFP were expressed in approximately 20% of ES-HPC. While expression of HNF-3, 4 and 6 reached levels similar to adult hepatocytes, ALB and AFP expression was several orders of magnitude lowerthan in adult tissue or cells. Stages of liver organogenesis are characterized by specific expression patterns of developmentally regulated genes. With sophisticated differentiation protocols, hepatic gene expression can be induced in a proportion of ES cells with gene expression patterns similar to early fetal liver.
Authors:
Andrea Jochheim; Tina Hillemann; Gabriela Kania; Jennifer Scharf; Masoumeh Attaran; Michael P Manns; Anna M Wobus; Michael Ott
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The International journal of developmental biology     Volume:  48     ISSN:  0214-6282     ISO Abbreviation:  Int. J. Dev. Biol.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-03-09     Completed Date:  2004-09-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8917470     Medline TA:  Int J Dev Biol     Country:  Spain    
Other Details:
Languages:  eng     Pagination:  23-9     Citation Subset:  IM    
Affiliation:
Hannover Medical School, Center of Internal Medicine, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany.
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MeSH Terms
Descriptor/Qualifier:
Albumins / genetics
Animals
Animals, Newborn
Cell Differentiation
Fetus / cytology,  metabolism*
Gene Expression Profiling*
Hepatocytes / cytology*,  metabolism*
Liver / cytology*,  embryology*,  metabolism
Mice
Microscopy, Fluorescence
Phenotype
RNA, Messenger / genetics,  metabolism
Stem Cells / cytology*,  metabolism
Transcription Factors / genetics
alpha-Fetoproteins / genetics
Chemical
Reg. No./Substance:
0/Albumins; 0/RNA, Messenger; 0/Transcription Factors; 0/alpha-Fetoproteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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