Single-cell transcriptomic analysis of mouse liver reveals nonparenchymal cells' intricate responses to PCB126 exposure
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ABSTRACT:
PROVIDER: PRJNA785801 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17111015_1.fastq.gz | Fastqsanger.gz | |||
| SRR17111015_2.fastq.gz | Fastqsanger.gz | |||
| SRR17111016_1.fastq.gz | Fastqsanger.gz | |||
| SRR17111016_2.fastq.gz | Fastqsanger.gz | |||
| SRR17111017_1.fastq.gz | Fastqsanger.gz |
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Project description:Polychlorinated biphenyls (PCBs) are ubiquitous and representative pollutants that pose great health risks. While cells' responses to dioxin-like PCBs tend to be studied on a bulk scale, few studies have been made from a single-cell level. Here, by using single-cell RNA sequencing, we depicted a detailed landscape of hepatic nonparenchymal cells' intricate responses to PCB126 exposure. A total of 13 clusters were identified. Notably, PCB126 exposure resulted in cell-type-specific gene expression profiles and genetic pathways. By analyzing genes related to aryl hydrocarbon receptors, we discovered that PCB126 induced the canonical genomic AhR pathway mainly in endothelial cells. In contrast, other cell types showed little induction. Enrichment pathway analysis indicated that immune cells changed their transcriptional patterns in response to PCB126. ScRNA-seq is a powerful tool to dissect underlying mechanisms of chemical toxicity regarding biological heterogeneity. Taken together, our study not only extends our current understanding of PCB126 toxicity, but also emphasizes the importance of in vivo cell heterogeneity in environmental toxicology.
2023-02-11 | GSE190084 | GEO
Project description:miRNA seq mouse liver HFD, PCB126, Aroclor1260 exposure
| PRJNA802236 | ENA
Project description:Exposure to polychlorinated biphenyls (PCBs) has been associated with liver injury in human cohorts and with nonalcoholic steatohepatitis (NASH) in mice fed a high fat diet (HFD). N(6)-methyladenosine (m6A) modification of mRNA regulates transcript fate, but the contribution of m6A modification on regulation of transcription in PCB-induced steatosis and fibrosis is unknown. This study tested the hypothesis that PCB and HFD exposure alters the levels of m6A modification in transcripts that play a role in NASH in vivo. Male C57Bl6/J mice were fed a HFD (12 wks.) and administered a single oral dose of Aroclor1260, PCB126, or Aroclor1260 + PCB126. Genome-wide identification of m6A peaks was accomplished by m6A mRNA immunoprecipitation sequencing (m6A-RIP) and the mRNA transcriptome identified by RNA-seq. Exposure of HFD-fed mice to Aroclor1260 decreased the number of m6A peaks and m6A-containing genes relative to HFD control whereas PCB126 or the combination of Aroclor1260+PCB126 increased m6A modification frequency. ~ 41% of genes had one m6A peak and ~49% had 2-4 m6A peaks. 117 m6A peaks were common in the four experimental groups. The Aroclor1260 + PCB126 exposure group showed the highest number (52) of m6A-peaks. qRT-PCR confirmed enrichment of m6A-containing fragments of the Apob transcript with PCB exposure. Integrated analysis of m6A-RIP-seq and mRNA-seq identified 242 differentially expressed genes (DEGs) with increased or reduced number of m6A peaks. Comparative pathway analysis identified “Immune response: IL-6-induced acute-phase response in hepatocytes” in the Aroclor1260 + PCB126 samples, consistent with steatohepatitis in human PCB epidemiological studies. These data show that PCB exposure in HFD-fed mice alters the m6A landscape offering an additional layer of regulation of gene expression affecting a subset of gene responses in NASH.
2023-05-12 | GSE202386 | GEO
Project description:This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD, PCB126 and PeCDF; the non-AhR ligand PCB153 and the binary mixture PCB126/PCB153 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg), PeCDF (200ng/kg), PCB126 (1000ng/kg) and PCB153 (1000ug/kg) 5 days a week for 13 weeks. Experiment Overall Design: There are 6 control chips and representing animals treated with vehicle control. There are 3 biological replicates (3 chips) for each treatment group (eg. TCDD, PCB126), each biological replicate is derived from 2 individual animals. A total of 21 chips were analyzed. Intensities were normalized using the GC-Robust Multiarray (GCRMA) method through Genetraffic software package.
2008-06-14 | E-GEOD-5789 | biostudies-arrayexpress
Project description:Exposure to high fat diet (HFD) and persistent organic pollutants including polychlorinated biphenyls (PCBs) is associated with liver injury in human populations and with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. Exposure of HFD-fed male mice to the non-dioxin-like (NDL) PCB mixture Aroclor1260 or to dioxin-like (DL) PCB126 or to the combination caused steatohepatitis and differentially altered the liver proteome with pathways involving epigenetic regulation of gene expression. Here unbiased RNA sequencing of miRNA (miRNA-seq) and subsequent network analysis to characterize the biological pathways altered by HFD and PCB exposure compared to HFD alone. Distinct miRNA expression patterns reveald a potential role of miRNAs in the pathogenesis of NAFLD. These results demonstrate miRNA and transcriptome pathways in PCB-related hepatic inflammation and fibrosis in a mouse model of NAFLD.
2024-04-23 | GSE195829 | GEO
Project description:Background: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been shown to alter and promote the development of alcohol-associated liver disease (ALD). Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in an ALD rodent model. Objectives: To better understand how PCB126 promoted ALD, the current study adopts transcriptomic and metallomic approaches to identify mechanistic pathways involved in this promotion. Methods: Briefly, male C57BL/6J mice were exposed to 0.2 mg/kg PCB126 or corn oil vehicle prior to ethanol feeding in the chronic-binge model. Liver tissues were collected for RNA sequencing and ICP-MS metals quantification. Results: PCB126 uniquely modified the transcriptome in EtOH-fed mice in terms of variance. EtOH feeding alone resulting in >4000 differentially expressed genes (DEGs) and PCB126 exposure resulted in more DEGs in the EtOH-fed group over the pair-fed group. Top gene ontology (GO) biological processes indicated ‘peptidyl tyrosine modifications’ and GO molecular function processes showed a loss of ‘metal, and ion, and zinc binding’. Western blot analysis depicted that the JAK2-STAT5 signaling axis was disrupted by the enhanced loss of phosphorylated JAK2 in EtOH+PCB126 mice. Quantified liver essential metal levels were overall depleted by EtOH feeding, and potassium, magnesium, cobalt, and zinc were further decreased by PCB126. Discussion: The results suggests that phosphorylation and metal binding are disrupted in EtOH+PCB126 mice, implying that evolutionarily conserved homeostatic signaling mechanisms are modified by pollutant exposure in EtOH-fed mice. The loss of phosphorylation and essential metals are two suggestive modes of action that may explain the promotion of disease by PCB126 in ALD.
2024-05-01 | GSE244388 | GEO
Project description:This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD, PCB126 and PeCDF; the non-AhR ligand PCB153 and the binary mixture PCB126/PCB153 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg), PeCDF (200ng/kg), PCB126 (1000ng/kg) and PCB153 (1000ug/kg) 5 days a week for 13 weeks. Keywords: Environmental pollutant toxicity comparison
2006-09-08 | GSE5789 | GEO
Project description:The objective of this study is to determine the effects of pre-conceptional exposure to environmental chemicals on DNA methylation and gene expression in testis. We used a dioxin-like PCB (3, 3’, 4, 4’, 5-pentachlorobiphenyl; PCB126) as a model environmental chemical because the mechanism of action is well-characterized, involving activation of aryl hydrocarbon receptor, a ligand-activated transcription factor. Adult zebrafish were exposed to 3 and 10 nM PCB126 for 24 h (water-borne exposure) and testis tissue was sampled at 7 days post-exposure for histology, DNA methylation and gene expression profiling. We used enhanced Reduced Representation Bisulfite Sequencing (RRBS) and RNAseq to quantify DNA methylation and gene expression, respectively. RRBS revealed 37 and 92 differentially methylated regions (DMRs) in response to 3 and 10nM PCB126 exposures, respectively. We observed 19 DMRs to be common between the two PCB126 treatment groups. Among them 14 and 5 are hypomethylated and hypermethylated, respectively. Majority of these DMRs are hypomethylated and gene ontology analysis revealed that these regions are regulate genes associated with RNA processing, nucleoside metabolic process, iron-sulfur cluster assembly and gluconeogenesis. Dysregulation of all these pathways have been associated with spermatogenic defects such as infertility. RNAseq results revealed differential expression of genes related to xenobiotic metabolism, oxidative stress and immune function. There was very little correlation between differentially methylated regions and differentially expressed genes suggesting complex and multiple layers of regulation. Overall, the results from this study provide new understanding about the mechanisms of action of dioxin-like PCBs in affecting testicular function and potential multigenerational phenotypes.
2021-12-15 | GSE190741 | GEO
Project description:There is growing evidence from epidemiological and experimental studies suggesting that early life exposure to environmental chemicals can have long-term consequences that are seen in adults and not apparent early in life. We recently demonstrated that developmental exposure of zebrafish embryos to low, non-embryotoxic levels of PCB126 did not affect larval behavior but caused changes in adult behavior (Glazer et al., 2016, NeuroToxicology 52:134-143). Zebrafish embryos were exposed to either vehicle (DMSO) or low concentrations of PCB126 (0.3, 0.6, 1.2 nM) for 20 h (4–24 h post fertilization), and then reared to adulthood in clean water. Locomotor activity of the larvae at 7 and 14 days post fertilization (dpf) was not affected by PCB126. In contrast, adult fish (4 months old) tested in novel tank and shoaling assays showed impaired habituation to a novel environment. In order to investigate the underlying molecular basis of these phenotypes, we determined the transcriptional profiles in whole embryos (48 hpf), larvae (5 dpf) and adult brain (4 mo) using strand-specific RNA-sequencing. Our results show that 0.3 nM PCB126 exposure induced cyp1a transcript levels 12.5-fold in 48-hpf embryos but there was no induction in 5-dpf larvae, suggesting transient activation of aryl hydrocarbon receptor during early development. No significant induction of cyp1a was observed in the brains of adults exposed as embryos to PCB126. However, we observed significant changes in gene expression profiles in the adult brain samples. A total of 2209 and 1628 genes were differentially expressed in 0.3 nM and 1.2 nM PCB126-exposed groups, respectively. KEGG pathway analysis of differentially expressed genes in the brain suggest enrichment of genes involved in oxidative phosphorylation, neurodegenerative diseases, circadian rhythm and calcium signaling pathways. We are currently investigating the role of these genes in altered behavior observed in the adults. Overall, our results suggest that PCB exposure during sensitive periods of early development alters normal development of the brain by reprogramming gene expression patterns. [Funded by NIH P01ES021923 and NSF OCE-1314642].
2017-08-10 | GSE98741 | GEO
Project description:The HC ToxArrayTM was used to analyze the hepatic gene expression profiles of male B6C3F1 mice exposed to PCB126.
2010-07-26 | E-MEXP-2701 | biostudies-arrayexpress