ArticleEnvironmental health perspectives
Disruption of aryl hydrocarbon receptor homeostatic levels during embryonic stem cell differentiation alters expression of homeobox transcription factors that control cardiomyogenesis.
Article in Environmental health perspectives. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- The aryl hydrocarbon receptor: structure, signaling, physiology and pathology.Signal transduction and targeted therapy · 2026Review
- Telmisartan potentiates the ITE-induced aryl hydrocarbon receptor activity in human liver cell line.Archives of toxicology · 2025Article
- Fine particulate matter‑induced cardiac developmental toxicity (Review).Experimental and therapeutic medicine · 2025Review
- The aryl hydrocarbon receptor directs the differentiation of murine progenitor blastomeres.Cell biology and toxicology · 2023Article
- TCDD alters essential transcriptional regulators of osteogenic differentiation in multipotent mesenchymal stem cells.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Genome-Wide ChIPseq Analysis of AhR, COUP-TF, and HNF4 Enrichment in TCDD-Treated Mouse Liver.International journal of molecular sciences · 2022Article
- Nuclear Receptors in Myocardial and Cerebral Ischemia-Mechanisms of Action and Therapeutic Strategies.International journal of molecular sciences · 2021Review
- Developmental and lifelong dioxin exposure induces measurable changes in cardiac structure and function in adulthood.Scientific reports · 2021Article
- Aryl hydrocarbon receptor: Its roles in physiology.Biochemical pharmacology · 2021Review
- How the AHR Became Important in Cancer: The Role of Chronically Active AHR in Cancer Aggression.International journal of molecular sciences · 2020Review
- Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes That Govern Cardiomyocyte Maturation.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- The AHR Signaling Attenuates Autoimmune Responses During the Development of Type 1 Diabetes.Frontiers in immunology · 2020Review
- Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells.The Science of the total environment · 2019Article
- Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- Aryl Hydrocarbon Receptor: A New Player of Pathogenesis and Therapy in Cardiovascular Diseases.BioMed research international · 2018Review
- Aryl Hydrocarbon Receptor Ablation in Cardiomyocytes Protects Male Mice From Heart Dysfunction Induced by NKX2.5 Haploinsufficiency.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Aryl hydrocarbon receptor (AHR): "pioneer member" of the basic-helix/loop/helix per-Arnt-sim (bHLH/PAS) family of "sensors" of foreign and endogenous signals.Progress in lipid research · 2017Review
- The aryl hydrocarbon receptor: a multifunctional chemical sensor for host defense and homeostatic maintenance.Experimental animals · 2017Review
- Does the Aryl Hydrocarbon Receptor Regulate Pluripotency?Current opinion in toxicology · 2017Article
- Genetic and Epigenetic Mechanisms Linking Air Pollution and Congenital Heart Disease.Journal of cardiovascular development and disease · 2016Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the expression of xenobiotic detoxification genes and is a critical mediator of gene-environment interactions. Many AHR target genes identified by genome-wide gene expression profiling have morphogenetic functions, suggesting that AHR may play a role in embryonic development.
objectivesTo characterize the developmental functions of the AHR, we studied the consequences of AHR activation by the agonist 2,3,7,8-tetrachlorodibenzo-p-doxin (TCDD), and the result of its repression by the antagonists 6,2,4-trimethoxyflavone and CH 223191 or by short-hairpin RNA (shRNA)-mediated Ahr knockdown during spontaneous differentiation of embryonic stem (ES) cells into cardiomyocytes.
methodsWe generated an AHR-positive cardiomyocyte lineage differentiated from mouse ES cells that expresses puromycin resistance and enhanced green fluorescent protein (eGFP) under the control of the Cyp1a1 (cytochrome P450 1a1) promoter. We used RNA sequencing (RNA.Seq) to analyze temporal trajectories of TCDD-dependent global gene expression in these cells during differentiation.
resultsActivation, inhibition, and knockdown of Ahr significantly inhibited the formation of contractile cardiomyocyte nodes. Global expression analysis of AHR-positive cells showed that activation of the AHR/TCDD axis disrupted the concerted expression of genes that regulate multiple signaling pathways involved in cardiac and neural morphogenesis and differentiation, including dozens of genes encoding homeobox transcription factors and Polycomb and trithorax group proteins.
conclusionsDisruption of AHR expression levels resulted in gene expression changes that perturbed cardiomyocyte differentiation. The main function of the AHR during development appears to be the coordination of a complex regulatory network responsible for attainment and maintenance of cardiovascular homeostasis.
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