Abstract
HepaRG cells, derived from a female hepatocarcinoma patient, are capable of differentiating into biliary epithelial cells and hepatocytes. More 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 with primary human hepatocytes and human liver tissues. To accomplish this objective, we used Affymetrix (Santa Clara, CA) U133 Plus 2.0 arrays to characterize the whole genome gene expression profiles in triplicate biological samples from HepG2 cells, 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 levels more similar to human primary hepatocytes and human liver tissues than HepG2 cells. In particular, many genes encoding drug-processing proteins are transcribed at a more similar level in HepaRG cells than in HepG2 cells compared with 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
This work was supported in part by the National Institutes of Health National Center for Research Resources [Grant P20-RR021940]; the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM087376]; Madison and Lila Self Graduate Fellowship from the University of Kansas (to S.N.H.); and University of Kansas Medical Center Biomedical Research Training Program (to Y.L.).
The Microarray Facility is supported by the Kansas University School of Medicine, KUMC Biotechnology Support Facility, the Smith Intellectual and Developmental Disabilities Research Center supported by the National Institutes of Health National Institute of Child Health and Human Development [Grant HD02528], and the Kansas IDeA Network of Biomedical Research Excellence supported by the National Institutes of Health National Center for Research Resources [Grant 2P20-RR016475].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.109.031831.
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The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
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ABBREVIATIONS:
- P450
- cytochrome P450
- UGT
- UDP glucuronosyltransferase
- GST
- glutathione transferase
- ADH
- alcohol dehydrogenase
- ALDH
- aldehyde dehydrogenase
- FMO
- flavin monooxygenase
- NAT
- N-acetyl transferase
- SULT
- sulfotransferase
- ABC
- ATP-binding cassette family
- SLCO
- solute carrier organic anion transporter family.
- Received December 17, 2009.
- Accepted March 12, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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