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Research ArticleArticle

A Comparison of Whole Genome Gene Expression Profiles of HepaRG Cells and HepG2 Cells to Primary Human Hepatocytes and Human Liver Tissues

Steven N. Hart, Ye Li, Kaori Nakamoto, Eva-anne Subileau, David Steen and Xiao-bo Zhong
Drug Metabolism and Disposition June 2010, 38 (6) 988-994; DOI: https://doi.org/10.1124/dmd.109.031831
Steven N. Hart
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Ye Li
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Kaori Nakamoto
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Eva-anne Subileau
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David Steen
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Xiao-bo Zhong
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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.

  • ↵Graphic The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

  • 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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Drug Metabolism and Disposition: 38 (6)
Drug Metabolism and Disposition
Vol. 38, Issue 6
1 Jun 2010
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Research ArticleArticle

A Comparison of Whole Genome Gene Expression Profiles of HepaRG Cells and HepG2 Cells to Primary Human Hepatocytes and Human Liver Tissues

Steven N. Hart, Ye Li, Kaori Nakamoto, Eva-anne Subileau, David Steen and Xiao-bo Zhong
Drug Metabolism and Disposition June 1, 2010, 38 (6) 988-994; DOI: https://doi.org/10.1124/dmd.109.031831

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Research ArticleArticle

A Comparison of Whole Genome Gene Expression Profiles of HepaRG Cells and HepG2 Cells to Primary Human Hepatocytes and Human Liver Tissues

Steven N. Hart, Ye Li, Kaori Nakamoto, Eva-anne Subileau, David Steen and Xiao-bo Zhong
Drug Metabolism and Disposition June 1, 2010, 38 (6) 988-994; DOI: https://doi.org/10.1124/dmd.109.031831
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