ArticleToxicological sciences : an official journal of the Society of Toxicology2011
Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro hazard assessment of chemical carcinogenicity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 62 citations in OpenAlex.
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- Assessment of Drugs Toxicity and Associated Biomarker Genes Using Hierarchical Clustering.Medicina (Kaunas, Lithuania) · 2019Article
- Toxic Dose prediction of Chemical Compounds to Biomarkers using an ANOVA based Gene Expression Analysis.Bioinformation · 2018Article
- Robust Co-clustering to Discover Toxicogenomic Biomarkers and Their Regulatory Doses of Chemical Compounds Using Logistic Probabilistic Hidden Variable Model.Frontiers in genetics · 2018Article
- Network and Pathway Analysis of Toxicogenomics Data.Frontiers in genetics · 2018Article
- Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury.Hepatology (Baltimore, Md.) · 2017Review
- Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity.Scientific reports · 2017Article
- Premalignant alteration assessment in liver-like tissue derived from embryonic stem cells by aristolochic acid I exposure.Oncotarget · 2016Article
- Analyzing and interpreting genome data at the network level with ConsensusPathDB.Nature protocols · 2016Article
- Xeno-sensing activity of the aryl hydrocarbon receptor in human pluripotent stem cell-derived hepatocyte-like cells.Scientific reports · 2016Article
- One Standardized Differentiation Procedure Robustly Generates Homogenous Hepatocyte Cultures Displaying Metabolic Diversity from a Large Panel of Human Pluripotent Stem Cells.Stem cell reviews and reports · 2016Article
- Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines.Stem cells international · 2016Article
- ToxDB: pathway-level interpretation of drug-treatment data.Database : the journal of biological databases and curation · 2016Article
- Stem cell-derived liver cells for drug testing and disease modeling.Discovery medicine · 2015Review
- MicroRNA-122: a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Computational modeling of drug response with applications to neuroscience.Dialogues in clinical neuroscience · 2014Review
- Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?EXCLI journal · 2014Article
- Modeling human liver biology using stem cell-derived hepatocytes.International journal of molecular sciences · 2013Review
- Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?British journal of clinical pharmacology · 2013Review
- Hepatic differentiation and maturation of human embryonic stem cells cultured in a perfused three-dimensional bioreactor.Stem cells and development · 2013Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte-like cells derived from the differentiation of human embryonic stem cells (hES-Hep) have potential to provide a human relevant in vitro test system in which to evaluate the carcinogenic hazard of chemicals. In this study, we have investigated this potential using a panel of 15 chemicals classified as noncarcinogens, genotoxic carcinogens, and nongenotoxic carcinogens and measured whole-genome transcriptome responses with gene expression microarrays. We applied an ANOVA model that identified 592 genes highly discriminative for the panel of chemicals. Supervised classification with these genes achieved a cross-validation accuracy of > 95%. Moreover, the expression of the response genes in hES-Hep was strongly correlated with that in human primary hepatocytes cultured in vitro. In order to infer mechanistic information on the consequences of chemical exposure in hES-Hep, we developed a computational method that measures the responses of biochemical pathways to the panel of treatments and showed that these responses were discriminative for the three toxicity classes and linked to carcinogenesis through p53, mitogen-activated protein kinases, and apoptosis pathway modules. It could further be shown that the discrimination of toxicity classes was improved when analyzing the microarray data at the pathway level. In summary, our results demonstrate, for the first time, the potential of human embryonic stem cell--derived hepatic cells as an in vitro model for hazard assessment of chemical carcinogenesis, although it should be noted that more compounds are needed to test the robustness of the assay.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.