Homo sapiens
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PROVIDER: PRJNA1256510 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Single-cell Transcriptomic Profiling of Chemicals in HepaRG Cells Using TempO-LINC
| PRJNA1257908 | ENA
Project description:These datasets are associated with the application of a novel genomics platform, TempO-LINC, for conducting high-throughput transcriptomic analysis on single cells and nuclei. The approach is fundamentally different than almost all other single-cell transcriptome profiling methods in that it does not rely on reverse transcription of mRNA. Instead, TempO-LINC is a novel combination of sensitive oligonucleotide ligation-based chemistry and highly scalable combinatorial barcoding. In this study, we applied TempO-LINC to profile the transcriptomes of multiple sample types. The data demonstrated the ability to identify and annotate at least 50 unique cell populations and positively correlate expression of cell type-specific molecular markers within them. TempO-LINC is a robust new single-cell technology that is ideal for large-scale applications/studies with high data quality.
2025-01-02 | GSE275129 | GEO
Project description:This study used high-throughput transcriptomics (HTTr) to evaluate the gene expression effects of 133 per- and polyfluoroalkyl substances (PFAS) in HepaRG cells. The PFAS chemicals were selected using a category-based prioritization approach developed by the U.S. Environmental Protection Agency (EPA) to ensure representation of structurally diverse compounds with relevance to human exposure and regulatory interest (Patlewicz et al., 2019; https://doi.org/10.1289/EHP4555). Differentiated HepaRG cells were exposed to each PFAS in concentration-response format (0.1 to 100 µM) for 24 hours. Transcriptomic changes were measured using the TempO-Seq platform (BioSpyder Technologies), enabling expression profiling of approximately 20,000 human genes. The resulting gene expression data were used to characterize the concentration-dependent molecular responses to PFAS exposure using connectivity mapping and to derive transcriptomic points of departure (tPODs). This dataset contributes to a broader effort to screen the bioactivity of environmental chemicals using HTTr in human liver-derived cells. It supports the use of transcriptomic profiling to identify bioactive PFAS, elucidate affected molecular pathways, and inform chemical hazard assessment.
2025-11-21 | GSE296248 | GEO
Project description:With thousands of chemicals in commerce and the environment, rapid identification of potential hazards is a critical need. Combining broad molecular profiling with targeted in vitro assays, such as high-throughput transcriptomics (HTTr) and receptor screening assays, could improve identification of chemicals that perturb key molecular targets associated with adverse outcomes. We aimed to link transcriptomic readouts to individual molecular targets and integrate transcriptomic predictions with orthogonal receptor-level assays in a proof-of-concept framework for chemical hazard prioritization. Transcriptomic profiles generated via TempO-Seq in U-2 OS and HepaRG cell lines were used to develop signatures comprised of genes uniquely responsive to reference chemicals for distinct molecular targets. These signatures were applied to 75 reference and 1,126 non-reference chemicals screened via HTTr in both cell lines. Selective bioactivity towards each signature was determined by comparing potency estimates against the bulk of transcriptomic bioactivity for each chemical. Chemicals predicted by transcriptomics were confirmed for target bioactivity and selectivity using available orthogonal assay data from US EPA’s ToxCast program. A subset of 37 selectively acting chemicals from HTTr that did not have sufficient orthogonal data were prospectively tested using one of five receptor-level assays. Of the 1,126 non-reference chemicals screened, 201 demonstrated selective bioactivity in at least one transcriptomic signature, and 57 were confirmed as selective nuclear receptor agonists. Chemicals bioactive for each signature were significantly associated with orthogonal assay bioactivity, and signature-based points-of-departure were equally or more sensitive than biological pathway altering concentrations in 81.2% of signature-prioritized chemicals. Prospective profiling found that 18 of 37 (49%) chemicals without prior orthogonal assay data were bioactive against the predicted receptor. Our work demonstrates that integrating transcriptomics with targeted orthogonal assays in a tiered framework can support Next Generation Risk Assessment by informing putative molecular targets and prioritizing chemicals for further testing. NOTE: this GEO entry only includes the HepaRG cell line data; the U-2 OS cell line data can be located via GEO accession number GSE274318.
2025-03-25 | GSE284321 | GEO
Project description:Introduction: Higher-throughput mode-of-action-based assays provide a valuable approach to expedite chemical evaluation for human health risk assessment. In this study, we combined the high-throughput alkaline CometChip® assay with the TGx-DDI transcriptomic biomarker (DDI = DNA damage-inducing) using high-throughput TempO-Seq® as an integrated genotoxicity testing approach. Objective: To determine if the high-throughput CometChip® assay and TGx-DDI biomarker analysis can be combined using human HepaRG™ cells to provide an efficient next-generation genotoxicity screening approach to identify DNA damage-inducing (DDI) chemicals. Methods: Metabolically competent human HepaRG™ cell cultures were exposed to increasing concentrations of 12 chemicals (9 DDI and 3 non-DDI) using a repeat exposure design (0 hr, 24 hr, 48 hr) in 96-well plates to measure and classify chemicals based on their ability to damage DNA. After a 4 hr recovery period, exposed cells were used to perform the Trevigen CometChip assay to assess DNA damage or used for TempO-Seq® S1500+ Targeted Transcriptome Sequencing for TGx-DDI classification purposes. Bioinformatics and statistical tools were used to classify chemicals as DDI or non-DDI using three separate analyses. Benchmark concentration analysis was also conducted for both assays for the purposes of potency ranking. Results: In combination, the CometChip® assay and the TGx-DDI were 100% accurate in identifying chemicals that induce DNA damage. Quantitative benchmark concentration (BMC) modeling was applied to evaluate chemical potencies for both assays. The BMCs for the CometChip® assay and the TGx-DDI for all 12 chemicals were highly concordant (within four-fold) and resulted in identical potency rankings. Conclusions: These results suggest that these two assays can be integrated for efficient, high-throughput identification of DNA damage in HepaRG™ cells. This study provides evidence for the complementarity of the high-throughput CometChip® assay with TGx-DDI biomarker analysis. Integration of these two tests provides an effective and high-throughput approach to identify DDI agents. This work is a first step in accomplishing a more integrated genotoxicity testing strategy to derive mechanistic information to better inform human health risk assessment in a high-throughput manner.
2021-07-21 | GSE171360 | GEO
Project description:This study used high-throughput transcriptomics (HTTr) to profile the concentration-dependent gene expression responses of ~300 reference chemicals with well-characterized mechanisms of action in differentiated HepaRG cells. The chemical set was selected to span a broad range of known molecular targets and biological response pathways. Cells were exposed to each chemical in a 7-point concentration-response format (0.1?100 µM) for 24 hours, and transcriptomic changes were measured using the TempO-Seq human whole transcriptome version 2 (hWTv2) assay (~20,000 genes). The objective of this study was to develop a compendium of transcriptional profiles from mechanistically annotated reference chemicals to support interpretation of HTTr data from uncharacterized compounds. These profiles enable identification of gene expression signatures associated with specific molecular targets and pathways, and allow evaluation of concentration-dependent activation patterns across pathways. This dataset provides a foundation for linking chemical exposures to biological mechanisms, informing hazard characterization, and supporting predictive toxicology. Keywords: Expression profiling by high throughput sequencing
2026-05-31 | GSE296254 | GEO
Project description:The experiment investigates the effects of five well-known chemicals on the transcriptome of the HepaRG cell line, a metabolically competent hepatic cell line. The cells were treated individually with an increasing concentrations of aflatoxin B1, benzo[a]pyrene, cyclosporine A, rotenone or trichostatin A at five exposure time points followed by targeted RNA-seq using TempO-Seq technology (the panel of human whole transcriptome). The aim of the study was to explore how and to what extent the point-of-departure (POD) obtained from an in vitro transcriptomics study varied as a function of exposure time.
2023-08-01 | E-MTAB-13168 | biostudies-arrayexpress
Project description:High-Throughput Transcriptomic Profiling of Tox21 Chemicals for Molecular Targets and Potency in HepaRG Cells
| PRJNA1254782 | ENA
Project description:High-Throughput Transcriptomic Profiling of PFAS Chemicals for Molecular Targets and Potency in HepaRG Cells
| PRJNA1254200 | ENA
Project description:Rapidly increasing number of man-made chemicals urges the development of reliable time- and cost-effective approaches for the carcinogen detection and identification. Considering this, the utility of high throughput microarray gene expression profiling for the identification of genotoxic and non-genotoxic carcinogens in vitro was investigated. Human terminally differentiated hepatic HepaRG cells were treated with model liver carcinogens, genotoxic carcinogen aflatoxin B1 (AFB1) and non-genotoxic carcinogen methapyrilene, at IC10 and IC25 concentrations for 72 hours, and transcriptomic profiles were determined. Treatment of HepaRG cells with IC10 and IC25 concentrations of AFB1 resulted in altered expression of 538 and 3033 genes (p-value ≤0.01 and fold change ≥2.0), respectively, and treatment of HepaRG cells with methapyrilene at the IC10 and IC25 concentrations altered the expression of 1255 and 1861 genes, respectively. Pathway analysis of transcriptomic signatures in HepaRG cells treated with minimally cytotoxic IC10 concentrations of AFB1 and methapyrilene demonstrated a strong enrichment in genes involved in key carcinogen-associated pathways, including receptor-mediated effects, detoxification response, cell death and apoptosis, cell proliferation and survival, oxidative stress and inflammation. Importantly, DNA damage and repair, cell cycle progression, and cell cycle checkpoint control pathways were uniquely activated in AFB1-treated HepaRG cells, whereas receptor-mediated signaling detoxification response pathway was predominantly altered in methapyrilene-treated HepaRG cells. In summary, high throughput microarray gene expression approach identifies specific carcinogen-exposure-associated transcriptomic responses and identifies affected molecular pathways, and categorize pathways associated with carcinogen exposure in a short-term in vitro test.
2016-09-17 | GSE87028 | GEO