An in vitro model of human hematopoiesis identifies a regulatory role for the aryl hydrocarbon receptor
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE224172 | GEO | 2023/11/13
REPOSITORIES: GEO
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Project description:Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of various environmental contaminants, like polycyclic and halogenated aromatic hydrocarbons, including the most potent agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we studied the effect of AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. . We show that AHR is differentially regulated in distinct lineages, provide evidence that TCDD impairs differentiation of hESCs and identify novel potential AHR target genes which expand our understanding on the role of this protein in different cell types.
2020-12-03 | GSE160981 | GEO
Project description:Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of various environmental contaminants, like polycyclic and halogenated aromatic hydrocarbons, including the most potent agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we studied the effect of AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. . We show that AHR is differentially regulated in distinct lineages, provide evidence that TCDD impairs differentiation of hESCs and identify novel potential AHR target genes which expand our understanding on the role of this protein in different cell types.
2020-12-03 | GSE160980 | GEO
Project description:Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of various environmental contaminants, like polycyclic and halogenated aromatic hydrocarbons, including the most potent agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we studied the effect of AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. . We show that AHR is differentially regulated in distinct lineages, provide evidence that TCDD impairs differentiation of hESCs and identify novel potential AHR target genes which expand our understanding on the role of this protein in different cell types.
2020-12-03 | GSE160935 | GEO
Project description:We report mRNA sequencing from decidual stromal cells after 24 hours and 6 days treatment with Aryl Hydrocarbon Receptor (AHR) activators 100 µM L-kynurenine or 10 nM TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin)
2019-06-01 | GSE114552 | GEO
Project description:The aryl hydrocarbon receptor (AHR) mediates the toxic effects of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Frogs are very insensitive to the toxic effects of TCDD. Experiment Overall Design: XLK-WG cells (ATCC) were grown to ~90% confluence in RPMI-1640 media supplemented with 20% FBS at 29 degrees and 5% CO2. Cells were subsequently exposed to 100 nM TCDD, FICZ, or DMSO vehicle (0.25%) for 3 hr prior to extraction of total RNA. Experiment Overall Design: Study included three complete biological replicates of each treatment.
2009-07-05 | E-GEOD-16670 | biostudies-arrayexpress
Project description:Conventional biochemical and molecular techniques identified previously several genes whose expression is regulated by the aryl hydrocarbon receptor (AHR). We sought to map the complete spectrum of AHR-dependent genes in male adult liver using expression arrays to contrast mRNA profiles in Ahr-null mice (Ahr–/–) with those in mice with wild-type AHR (Ahr+/+). Transcript profiles were determined both in untreated mice and in mice treated 19 h earlier with 1000 µg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of 456 ProbeSets was significantly altered by TCDD in an AHR-dependent manner, including members of the classic AHRE-I gene battery, such as Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1. In the absence of exogenous ligand, AHR status alone affected expression of 392 ProbeSets, suggesting that the AHR has multiple functions in normal physiology. In Ahr–/– mice, only 32 ProbeSets exhibited responses to TCDD, indicating that the AHR is required for virtually all transcriptional responses to dioxin exposure in liver. The flavin-containing monooxygenases, Fmo2 and Fmo3, considered previously to be uninducible, were highly induced by TCDD in an AHR-dependent manner. The estrogen receptor alpha as well as two estrogen-receptor-related genes (alpha and gamma) exhibit AHR-dependent expression, thereby extending cross-talk opportunities between the intensively studied AHR and estrogen receptor pathways. p53 binding sites are over-represented in genes down-regulated by TCDD, suggesting that TCDD inhibits p53 transcriptional activity. Overall, our study identifies a wide range of genes that depend on the AHR, either for constitutive expression or for response to TCDD. Keywords: treatment-control and mutant-wildtype
2008-11-01 | GSE10082 | GEO
Project description:Major toxicities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) result from dysregulation of gene expression mediated by the aryl hydrocarbon receptor (AHR). Dioxin-like chemicals alter expression of numerous genes in liver but the specific genes whose dysregulation leads to toxicities such as wasting, hepatotoxicity and lethality have not been identified. We searched for genes that are most likely to be key to dioxin toxicity by using gene expression arrays to contrast hepatic gene expression after TCDD treatment in dioxin-sensitive rats (that carry wildtype AHR) with gene expression in H/W(Kuopio) rats which are highly resistant to dioxin toxicity due to a major deletion in the AHR's transactivation domain (TAD). The total number of TCDD-responsive genes was smaller in rats with the AHRH/W genotype than in rats with wildtype AHR. However, genes in the classic AH gene battery such as CYP1A1, CYP1A2 and CYP1B1 remained fully responsive to TCDD in AHRH/W rats; thus the TAD deletion selectively interferes with expression of a subset of hepatic genes rather than abolishing global AHR-mediated responses. Genes in the following functional categories differ in response to TCDD between dioxin-sensitive rats and dioxin-resistant rats: fatty acid oxidation, metabolism (xenobiotic, alcohol, amino acid, and fatty acid), phosphate transport, regulation of steroid biosynthesis, nitrogen compound catabolism, and generation of precursor metabolites and energy. Many of these differentially-responsive genes are integral parts of pathways such as: protein degradation and synthesis, fatty acid metabolism and synthesis, cytokinesis, cell growth, and apoptosis which may be part of mechanisms which lead to TCDD-induced wasting, hepatotoxicity, tumors, and death. These differentially-responsive genes are worthy candidates for further mechanistic studies to test their role in mediating or protecting from major dioxin toxicities. Experiment Overall Design: Four strains of rats were either treated with 100 ug/kg TCDD or cornoil vehicle and profiled at 19 hours, each with four replicates. Two strains were also analyzed at 3 hours, each with four replicates.
2009-12-02 | E-GEOD-10083 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters differentiation of B cells and suppresses antibody production. The objectives of this study was to use a combination of whole genome, microarray-based chromatin immunoprecipitation (ChIP-on-chip) and time course gene expression microarray analysis on the mouse B-cell line CH12.LX following exposure to lipopolysaccharide (LPS) or LPS and TCDD to identify the primary and downstream transcriptional elements of B-cell differentiation that are altered by the AHR.
2010-09-01 | GSE23708 | GEO
Project description:Major toxicities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) result from dysregulation of gene expression mediated by the aryl hydrocarbon receptor (AHR). Dioxin-like chemicals alter expression of numerous genes in liver but the specific genes whose dysregulation leads to toxicities such as wasting, hepatotoxicity and lethality have not been identified. We searched for genes that are most likely to be key to dioxin toxicity by using gene expression arrays to contrast hepatic gene expression after TCDD treatment in dioxin-sensitive rats (that carry wildtype AHR) with gene expression in H/W(Kuopio) rats which are highly resistant to dioxin toxicity due to a major deletion in the AHR's transactivation domain (TAD). The total number of TCDD-responsive genes was smaller in rats with the AHRH/W genotype than in rats with wildtype AHR. However, genes in the classic AH gene battery such as CYP1A1, CYP1A2 and CYP1B1 remained fully responsive to TCDD in AHRH/W rats; thus the TAD deletion selectively interferes with expression of a subset of hepatic genes rather than abolishing global AHR-mediated responses. Genes in the following functional categories differ in response to TCDD between dioxin-sensitive rats and dioxin-resistant rats: fatty acid oxidation, metabolism (xenobiotic, alcohol, amino acid, and fatty acid), phosphate transport, regulation of steroid biosynthesis, nitrogen compound catabolism, and generation of precursor metabolites and energy. Many of these differentially-responsive genes are integral parts of pathways such as: protein degradation and synthesis, fatty acid metabolism and synthesis, cytokinesis, cell growth, and apoptosis which may be part of mechanisms which lead to TCDD-induced wasting, hepatotoxicity, tumors, and death. These differentially-responsive genes are worthy candidates for further mechanistic studies to test their role in mediating or protecting from major dioxin toxicities. Keywords: Treatment-Control, Inter-Strain, Time-Course
2009-11-24 | GSE10083 | GEO
Project description:The aryl hydrocarbon receptor (AHR) mediates the toxic effects of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Frogs are very insensitive to the toxic effects of TCDD.
2009-06-24 | GSE16670 | GEO