RNA-sequencing of 14 diverse mouse strains treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA704322 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13770000_1.fastq.gz | Fastqsanger.gz | |||
| SRR13770000_2.fastq.gz | Fastqsanger.gz | |||
| SRR13770100_1.fastq.gz | Fastqsanger.gz | |||
| SRR13770100_2.fastq.gz | Fastqsanger.gz | |||
| SRR13770001_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 336 |
Similar Datasets
Project description:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor in the PAS superfamily of environmental sensors that is linked to several metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). Much remains unknown regarding the impact of genetic variation in AHR-driven disease, as past studies have focused on a small number of inbred strains. Recently, the presence of a wide-range of interindividual variability amongst humans was reported in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypical ligand of the AHR. In this study, a panel of 14 diverse mouse strains were exposed to TCDD for 10 days to characterize the AHR-mediated response across genetic backgrounds. In this study, responses to TCDD are heavily-dependent on genetic background. While mice carry one of four Ahr alleles that impact the AHR-mediated responses, we observed significant intra-allelic variability suggesting the presence of novel genetic modifiers of AHR signaling. A regression-based approach was used to scan for genes regulated by the AHR and/or associated with TCDD-induced phenotypes. The approach identified seven genes, 2 of which are novel, that are likely regulated by the AHR based on association with hepatic TCDD burden (p≤0.05). Finally, we identified a gene, Dio1, which was associated with change in percent body fat across the diverse set of strains (p≤0.05). Overall, the results in this study exemplify the power of genetics-based approaches in identifying novel genes that are putatively regulated by the AHR.
2021-05-01 | GSE167328 | GEO
Project description:Dose-dependent jejunal epithelial gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on jejunal differential gene expression, in order to investigate the role of the jejunum in TCDD-elicited steatohepatitis in C57BL/6.
2015-10-01 | GSE70379 | GEO
Project description:Alternative splicing is a co-transcriptional mechanism by including or excluding exons in different combinations, thereby expanding the diversity of protein isoforms of a single gene. Abnormalities in this process can result in deleterious effects to human health, and several xenobiotics are known to interfere with splicing regulation through multiple mechanisms. These changes could lead to human diseases such as cancer, neurological disorders, autoimmune diseases, and developmental disorders. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant generated as a byproduct of various industrial activities. Exposure to this dioxin has been linked to a wide range of pathologies through the alteration of multiple cellular processes. However, the effects of TCDD exposure on alternative splicing have not yet been studied. Here, we investigate whether exposure to TCDD influenced hepatic alternative splicing in adult male C57BL/6J mice. We identified several genes whose alternative splicing of precursor messenger RNAs was modified following TCDD exposure. In particular, we demonstrated that alternative splicing of Cyp1a1, Ahrr, and Actn1 was significantly altered after TCDD treatment. These findings show that exposure to TCDD has an impact on alternative splicing, presumably through binding to the aryl hydrocarbon receptor, and suggest a new avenue for AhR-mediated pathogenesis.
2019-10-29 | GSE126328 | GEO
Project description:A toxicogenomics approach was used to qualitatively and quantitatively compare the gene expression changes in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatocytes from five individual rats and five individual humans were exposed for 24 hours to 11 concentrations of TCDD ranging from 0.00001 nM to 100 nM and a vehicle control. Gene expression changes were analyzed using whole genome microarrays.
2012-02-03 | GSE34250 | GEO
Project description:A toxicogenomics approach was used to qualitatively and quantitatively compare the gene expression changes in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatocytes from five individual rats and five individual humans were exposed for 24 hours to 11 concentrations of TCDD ranging from 0.00001 nM to 100 nM and a vehicle control. Gene expression changes were analyzed using whole genome microarrays.
2012-02-03 | GSE34249 | GEO
Project description:Exposure to dioxins has been associated with impaired development of the nervous system and losses of brain functions. However, the precise cellular events and related molecular basis underlining these adverse effects has not been fully understood. We aimed to reveal global alterations of mRNA expression and potential cellular events by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.
2020-07-12 | GSE101464 | GEO
Project description:Oxidative stress is an important mechanism of chemical toxicity, contributing to teratogenesis as well as to cardiovascular and neurodegenerative diseases. Developing animals may be especially sensitive to chemicals causing oxidative stress. To assess the response to chemicals at different stages of development, zebrafish (Danio rerio) embryos at 1, 2, 3, 4, 5, and 6 days post-fertilization (dpf) were exposed to 0.1% dimethyl sulfoxide (DMSO), 2 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or 10 uM tert-butylhydroquinone (tBHQ) for 6 hr. Transcript abundance was assessed by real-time qRT-PCR and microarray (Agilent 22k). By microarray, 1477 probes were significantly different among the DMSO-, tBHQ-, and TCDD-treated embryos at 4 dpf. Of these, 220 were 2-fold or greater up-regulated and 108 were 2-fold or greater down-regulated by tBHQ. For TCDD, 17 probes were 2-fold or greater up-regulated and 6 were 2-fold or greater down-regulated. Genes induced by tBHQ, included genes involved in glutathione synthesis and utilization, signal transduction, and DNA damage / stress response. Keywords: Danio rerio, TCDD, tBHQ, oxidative stress, gene expression Separate groups of 30 embryos generated from TL adults were placed in 15 ml egg water in a 10-cm glass petri and at 1, 2, 3, 4, 5, and 6-dpf were exposed for 6 hr to 0.1% dimethyl sulfoxide (DMSO), 2 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or 10 uM tert-butylhydroquinone (tBHQ) (4 replicates per compound per time point). Embyros were frozen immediately after the 6 hr exposure and RNA isolated for microarray analysis. A Universal RNA Reference Sample was created by mixing equal amounts of total RNA from 2 replicates each from all toxicants (TCDD, tBHQ, DMSO) and timepoints (1, 2, 3, 4, 5, 6-dpf). Based on qRT-PCR results, the 4 dpf timepoint was selected for microarray analysis, in which the RNA samples (4 replicates per compound) were Cy3 labeled and co-hybridized with Cy5 labeled Universal RNA Reference Sample to generate data for analysis of variance.
2010-04-03 | E-GEOD-10157 | biostudies-arrayexpress
Project description:Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to disrupt many physiological processes including hepatic lipid metabolism, bile acid homeostasis, glucose metabolism, iron and heme homeostasis, and one-carbon metabolism. TCDD disrupts these metabolic pathways mediated by the aryl hydrocarbon receptor (AhR). We have previously shown that the AhR localizes to genomic regions possessing DNA motifs that also contain binding sites for other transcription factors, implicating potential co-operation between the AhR and these other transcription factors in the regulation of target genes. Two possible co-operating transcription factors include HNF4α and COUP-TFII. To investigate interactions between AhR, HNF4α and COUP-TFII hepatic ChIP-seq analysis was performed for HNF4α and COUP-TFII mice treated with TCDD for 2 hours, to supplement pre-existing AhR ChIP-seq data. ChIP-seq analysis revealed genome-wide changes in COUP-TFII and HNF4α binding following treatment with TCDD, with 11,688 and 9,547 genomic regions possessing differential enrichment, respectively. These differentially enriched regions for COUP-TFII and HNF4α fell within the intragenic region of 6,846 and 5,762 genes, respectively. When supplemented with pre-existing AhR ChIP-seq data, AhR, HNF4α and COUP-TFII were found to co-bind to the intragenic region of 6,376 genes.
2021-08-03 | GSE178168 | GEO
Project description:Dose-response hepatic single nuclei RNA sequencing of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated mice
| PRJNA764849 | ENA
Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant that disrupts normal hepatic function. This disruption leads to the development and progression of non-alcoholic fatty liver disease (NAFLD) pathologies, including steatosis, steatohepatitis, and fibrosis. TCDD exerts hepatotoxic effects through activation of the aryl hydrocarbon receptor (AHR) eliciting transcriptional changes. Although diverse liver cell types contribute to TCDD-induced hepatotoxicity, cell-specific transcriptional changes in response to acute TCDD exposure remain unclear. The objective of this project was to elucidate the cell-specific outcomes of AHR activation following acute TCDD exposure. We conducted liver single-nuclei RNA-sequencing from male C57BL/6 mice administered 30 μg/kg of TCDD or sesame oil and sacrificed at 2, 4, 8, 12, 18, 24, or 72 hours post-oral gavage. Leiden clustering and annotation identified 10 major liver cell types, and 2 macrophage and 8 endothelial cell (EC) subtypes. While most cell types maintained their relative abundance, neutrophils exhibited an increase at 72 hours in response to TCDD. Hepatocytes, ECs, and hepatic stellate cells (HSCs) were the only cell types with cell-specific gene expression changes with known AHR binding sites (1,550, 102, and 40, respectively). Functional enrichment analysis in response to TCDD revealed disruptions in the metabolism of steroids, primary bile acids, vitamins, retinols, and glutathione in addition to one-carbon metabolism. EC differential gene expression was associated with PI3-AKT signaling, as well as protein processing and transport pathways. HSCs were enriched in protein processing, ABC transporters, and the dysregulation of tryptophan and linoleic acid metabolism. Altogether, these results suggest that early responses to TCDD trigger cell-specific changes in gene expression in the liver, contributing to hepatotoxicity and the emergence of hepatic pathologies related to NAFLD.
2024-08-20 | GSE254121 | GEO