RT Journal Article
SR Electronic
T1 Interindividual Variability in Gene Expression Profiles in Human Hepatocytes and Comparison with HepaRG Cells
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 151
OP 158
DO 10.1124/dmd.111.042028
VO 40
IS 1
A1 Alexandra Rogue
A1 Carine Lambert
A1 Catherine Spire
A1 Nancy Claude
A1 André Guillouzo
YR 2012
UL http://dmd.aspetjournals.org/content/40/1/151.abstract
AB Interindividual variations in functions other than drug metabolism activity, remain poorly elucidated in human liver. In the present study, the whole transcriptome of several human hepatocyte populations and the differentiated human HepaRG cell line have been analyzed and compared, using oligonucleotide pangenomic microarrays. We show that, although the variation in the percentages of expressed genes did not exceed 14% among the primary human hepatocyte populations, huge interindividual differences in the transcript levels of many genes were observed. These genes were related to various functions; in addition to drug metabolism, they mainly concerned carbohydrate, amino acid, and lipid metabolism. HepaRG cells expressed from 81 to 92% of the genes active in human hepatocytes and, in addition, a specific gene subset mainly related to their transformed status, some chromosomal abnormalities, and the presence of primitive biliary epithelial cells. Of interest, a relationship was evidenced between abnormal basal expression levels of some target genes and their corresponding previously reported fold changes in one of four human hepatocyte populations treated with the hepatotoxic drug troglitazone and not with other nonhepatotoxic peroxisome proliferator-activated receptor agonists (PLoS One 6:e18816, 2011). Taken together, our results support the view that HepaRG cells express most of the genes active in primary human hepatocytes and show that expression of most human hepatic genes can quantitatively greatly vary among individuals, thereby contributing to explain the huge interindividual variability in susceptibility to drugs and other environmental factors.