ArticlePloS one2015
Differences in the Epigenetic Regulation of Cytochrome P450 Genes between Human Embryonic Stem Cell-Derived Hepatocytes and Primary Hepatocytes.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 77 citations in OpenAlex.
- CYP2E1 and CYP2D6 in Anti-Tuberculosis Drug-Induced Liver Injury: Mechanisms, Epigenetic Regulation, and Translational Implications.Clinical and translational science · 2026Review
- Identification of Reactive Metabolites of Acetaminophen and Saxagliptin in Human Hepatocytes and Hepatic Organoids.Pharmaceutics · 2026Article
- Article
- Integrating Molecular Testing With Clinical Criteria and Histopathology Improves Diagnostic Precision in Immune-Mediated Liver Diseases.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Current hPSC-derived liver organoids for toxicity testing: Cytochrome P450 enzymes and drug metabolism.Toxicological research · 2025Review
- Amino Acid Hepatotoxicity Biomarkers in Human Hepatic Organoids: Promising Standardization of Drug Toxicity Evaluation.ACS pharmacology & translational science · 2025Article
- Epigenetics in pharmacogenes encoding metabolizing enzymes of second-generation antipsychotics used in schizophrenia and its clinical implications.Frontiers in pharmacology · 2025Review
- Age-Dependent Changes in Cytochrome P450 Abundance and Composition in Human Liver.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Clues of HLAs, metabolic SNPs, and epigenetic factors in T cell-mediated drug hypersensitivity reactions.Heliyon · 2024Review
- Precise Therapy Using the Selective Endogenous Encapsidation for Cellular Delivery Vector System.Pharmaceutics · 2024Review
- Expression and significance of histone methyltransferase SET domain containing 2 with histone H3 lysine 36 trimethylation in mouse hepatic oval cells differentiated into bile duct epithelial cellsMolecular medicine reports · 2023Article
- Human induced pluripotent stem cell-derived liver-on-a-chip for studying drug metabolism: the challenge of the cytochrome P450 family.Frontiers in pharmacology · 2023Review
- Comparing feature selection and machine learning approaches for predictingFrontiers in neuroinformatics · 2023Article
- Role of the soluble epoxide hydrolase in the hair follicle stem cell homeostasis and hair growth.Pflugers Archiv : European journal of physiology · 2022Article
- Cytochrome P450 Enzymes and Drug Metabolism in Humans.International journal of molecular sciences · 2021Review
- Dysregulated ECM remodeling proteins lead to aberrant osteogenesis of Costello syndrome iPSCs.Stem cell reports · 2021Article
- DNA methylation and histone acetylation changes to cytochrome P450 2E1 regulation in normal aging and impact on rates of drug metabolism in the liver.GeroScience · 2020Article
- Transcriptomic Profiles of MV4-11 and Kasumi 1 Acute Myeloid Leukemia Cell Lines Modulated by Epigenetic Modifiers Trichostatin A and 5-Azacytidine.International journal of hematology-oncology and stem cell research · 2020Article
- HBV-related hepatocarcinogenesis: the role of signalling pathways and innovative ex vivo research models.BMC cancer · 2019Review
- Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity.Pharmacology & therapeutics · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human pluripotent stem cell-derived hepatocytes have the potential to provide in vitro model systems for drug discovery and hepatotoxicity testing. However, these cells are currently unsuitable for drug toxicity and efficacy testing because of their limited expression of genes encoding drug-metabolizing enzymes, especially cytochrome P450 (CYP) enzymes. Transcript levels of major CYP genes were much lower in human embryonic stem cell-derived hepatocytes (hESC-Hep) than in human primary hepatocytes (hPH). To verify the mechanism underlying this reduced expression of CYP genes, including CYP1A1, CYP1A2, CYP1B1, CYP2D6, and CYP2E1, we investigated their epigenetic regulation in terms of DNA methylation and histone modifications in hESC-Hep and hPH. CpG islands of CYP genes were hypermethylated in hESC-Hep, whereas they had an open chromatin structure, as represented by hypomethylation of CpG sites and permissive histone modifications, in hPH. Inhibition of DNA methyltransferases (DNMTs) during hepatic maturation induced demethylation of the CpG sites of CYP1A1 and CYP1A2, leading to the up-regulation of their transcription. Combinatorial inhibition of DNMTs and histone deacetylases (HDACs) increased the transcript levels of CYP1A1, CYP1A2, CYP1B1, and CYP2D6. Our findings suggest that limited expression of CYP genes in hESC-Hep is modulated by epigenetic regulatory factors such as DNMTs and HDACs.
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