Abstract
HepaRG cells, derived from a female hepatocarcinoma patient, are capable of differentiating into biliary epithelial cells and hepatocytes. Importantly, differentiated HepaRG cells are able to maintain activities of many xenobiotic metabolizing enzymes and expression of the metabolizing enzyme genes can be induced by xenobiotics. The ability of these cells to express and induce xenobiotic-metabolizing enzymes is in stark contrast to the frequently used HepG2 cells. The previous studies have mainly focused on a set of selected genes; therefore, it is of significant interest to know the extent of similarity of gene expression at whole genome levels in HepaRG cells and HepG2 cells compared to primary human hepatocytes and human liver tissues. To accomplish this objective, we used Affymetrix U133 Plus 2.0 arrays to characterize the whole genome gene expression profiles in triplicate biological samples from HepG2 cells, and HepaRG cells (undifferentiated and differentiated cells), freshly isolated primary human hepatocytes, and frozen liver tissues. After using similarity matrix, principal components, and hierarchical clustering methods, we found that HepaRG cells globally transcribe genes at the levels more similar to human primary hepatocytes and human liver tissues than HepG2 cells. Particularly, many genes encoding drug processing proteins are transcribed at a more similar level in HepaRG cells than in HepG2 cells compared to primary human hepatocytes and liver samples. The transcriptomic similarity of HepaRG with primary human hepatocytes is encouraging for use of HepaRG cells in the study of xenobiotic metabolism, hepatotoxicology, and hepatocyte differentiation.
Footnotes
- Received December 21, 2009.
- Accepted March 12, 2010.
- The American Society for Pharmacology and Experimental Therapeutics