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

Hart, Steven N.; Li, Ye; Nakamoto, Kaori; Subileau, Eva Anne; Steen, David; Zhong, Xiao Bo

doi:10.1124/dmd.109.031831

Cited by 247 publications

(192 citation statements)

References 24 publications

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“…Recently, omics technologies have entered the field of toxicology, leading to toxicogenomics, a very powerful tool for studying the toxicity of substances using cellbased assays and for deciphering chemical modes of action (Hartung 2010;Jennings et al 2013;Pisani et al 2015). In particular, the transcriptomic similarity of HepaRG to primary human hepatocytes is encouraging for the use of this model to study xenobiotic metabolism and hepatotoxicity (Hart et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

et al. 2017

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Magnetic mesoporous silica nanoparticles (M-MSNs) are a promising class of nanoparticles for drug delivery. However, a deep understanding of the toxicological mechanisms of action of these nanocarriers is essential, especially in the liver. The potential toxicity on HepaRG cells of pristine, pegylated (PEG), and lipid (DMPC) M-MSNs were compared. Based on MTT assay and real-time cell impedance, none of these NPs presented an extensive toxicity on hepatic cells. However, we observed by transmission electron microscopy (TEM) that the DMPC and pristine M-MSNs were greatly internalized. In comparison, PEG M-MSNs showed a slower cellular uptake. Whole gene expression profiling revealed the M-MSNs molecular modes of action in a time-and dose-dependent manner. The lowest dose tested (1.6 mg/cm 2 ) induced no molecular effect and was defined as 'No Observed Transcriptional Effect level.' The dose 16 mg/cm 2 revealed nascent but transient effects. At the highest dose (80 mg/cm 2 ), adverse effects have clearly arisen and increased over time. The limit of biocompatibility for HepaRG cells could be set at 16 mg/cm 2 for these NPs. Thanks to a comparative pathway-driven analysis, we highlighted the sequence of events that leads to the disruption of hepatobiliary system, elicited by the three types of MMSNs, at the highest dose. The Adverse Outcome Pathway of hepatic cholestasis was implicated. Toxicogenomics applied to cell cultures is an effective tool to characterize and compare the modes of action of many substances. We propose this strategy as an asset for upstream selection of the safest nanocarriers in the framework of regulation for nanobiosafety. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

et al. 2017

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“…Olsavsky et al (2007) compared global gene expression profiles of HepG2, Huh7, human primary hepatocytes, and human liver slices. Hart et al (2010) recently compared whole-genome gene expression profiles of HepaRG cells and HepG2 cells with that of primary human hepatocytes and demonstrated that many DMETs are expressed at a level in HepaRG cells comparable to that in HepG2 cells in comparison with primary human hepatocytes. To overcome the disadvantages of a short life span and limited availability of primary human hepatocytes, immortalized "normal" human liver epithelial cell lines were established by introduction of the simian virus 40 large T antigen gene.…”

Section: Introductionmentioning

confidence: 99%

Similarities and Differences in the Expression of Drug-Metabolizing Enzymes between Human Hepatic Cell Lines and Primary Human Hepatocytes

Guo

Dial²,

Shi³

et al. 2010

Drug Metab Dispos

285

202

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ABSTRACT:In addition to primary human hepatocytes, hepatoma cell lines, and transfected nonhepatoma, hepatic cell lines have been used for pharmacological and toxicological studies. However, a systematic evaluation and a general report of the gene expression spectra of drug-metabolizing enzymes and transporters (DMETs) in these in vitro systems are not currently available. To fill this information gap and to provide references for future studies, we systematically characterized the basal gene expression profiles of 251 drugmetabolizing enzymes in untreated primary human hepatocytes from six donors, four commonly used hepatoma cell lines (HepG2, Huh7, SK-Hep-1, and Hep3B), and one transfected human liver epithelial cell line. A large variation in DMET expression spectra was observed between hepatic cell lines and primary hepatocytes, with the complete absence or much lower abundance of certain DMETs in hepatic cell lines. Furthermore, the basal DMET expression spectra of five hepatic cell lines are summarized, providing references for researchers to choose carefully appropriate in vitro models for their studies of drug metabolism and toxicity, especially for studies with drugs in which toxicities are mediated through the formation of reactive metabolites.

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“…NC, negative control; GTSF1, gametocyte specific factor 1; si, small interfering. these changes can affect protein concentrations and the copy number (24)(25)(26). Conversely, genetic changes involved in the development of liver cancer, the cancer protein secretomes and the biological significance of human leucocyte antigen expression in HCC tumors closely resemble those of the HepG2 cells observed in previous studies (27)(28)(29).…”

Section: Discussionmentioning

confidence: 49%

GTSF1 gene may serve as a novel potential diagnostic biomarker for liver cancer

et al. 2017

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Abstract. The gametocyte-specific factor 1 (GTSF1) gene participates in DNA methylation and retrotransposon activation in germ cells, particularly during cell proliferation. The present study aimed to assess the level of GTSF1 gene expression in liver cancer tumor tissues, and its role in human hepatoma cell lines in vitro and in a nude mouse model in vivo. GTSF1 gene expression was detected in liver cancer tumor tissues, compared with in healthy controls, via reverse transcription quantitative polymerase chain reaction. An adeno-associated virus vector was used to study tumor stem cell proliferation in vivo. A plasmid expressing GTSF1 was constructed and transfected into various human hepatoma cell lines, in order to analyze the cellular proliferation and apoptosis of liver cancer cells using small interfering (si)RNAs in vitro. In the present study, GTSF1 gene expression was detected in 18/24 (75.0%) liver cancer tumor tissues from patients with hepatocellular carcinoma (HCC), and elevated GTSF1 expression was identified in the tissue of one of 32 healthy control samples (3.13%; P<0.05). Notably, the GTSF1 gene was expressed at a higher frequency in AFP-positive HCC samples (14/16, 87.50%) compared with in AFP-negative HCC samples (4/8, 50.0%; P=0.129). In addition, there was no statistical significance between GTSF1 expression in non-HBV-infected (71.42%) and HBV-infected HCC specimens (76.47%), as determined by a χ 2 test (P=0.921). It was demonstrated that GTSF1 significantly increased the tumorigenicity of Ad-shNC-transfected (GTSF1-positive) HepG2 cells in the nude mouse xenograft model, whereas the sizes and weights of the tumors in the GTSF1-negative group were dercreased in comparison with the GTSF1-positive group (P<0.05). Reduced levels of GTSF1 mRNA, along with fewer and smaller colonies, were identified in two groups of human liver cancer cells treated with with GTSF1-targeting siRNA, when compared with cells without GTSF1 mRNA interference (P<0.05). In summary, the present study elucidated the GTSF1 mRNA expression pattern in liver cancer, and investigated the potential role of GTSF1 in tumorigenesis. The data suggest an important role for the GTSF1 gene in the molecular etiology of hepatocarcinogenesis, and indicate a potential application of GTSF1 mRNA expression in liver cancer diagnosis and therapy.

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

Cited by 247 publications

References 24 publications

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

Similarities and Differences in the Expression of Drug-Metabolizing Enzymes between Human Hepatic Cell Lines and Primary Human Hepatocytes

GTSF1 gene may serve as a novel potential diagnostic biomarker for liver cancer

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