Project description:This SuperSeries is composed of the following subset Series: GSE15857: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Kidney GSE15858: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Liver Refer to individual Series
Project description:Aryl hydrocarbon receptor ChIP-Seq performed in livers of female mice gavaged with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 2hrs
Project description:Aryl hydrocarbon receptor ChIP-Seq performed in livers of male mice gavaged with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 2hrs
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.
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)
Project description:Dioxin and dioxin-related polychlorinated biphenyls are potent toxicants with association with developmental heart defects and congenital heart diseases. However, the underlying mechanism of their developmental toxicity is not fully understood. Further, different animals show distinct susceptibility and phenotypes after exposure, suggesting possible species-specific effects. Using a human embryonic stem cell (ESC) cardiomyocyte differentiation model, we examined the impact, susceptible window, and dosage of 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD) on human cardiac development. We showed that treatment of human ESCs with TCDD at the ESC stage inhibits cardiomyocyte differentiation, and the effect is largely mediated by the aryl hydrocarbon receptor (AHR). We further identified genes that are differentially expressed after TCDD treatment by RNA-sequencing, and genomic regions that are occupied by AHR by chromatin immunoprecipitation and high-throughput sequencing. Our results support the model that TCDD impairs human ESC cardiac differentiation by promoting AHR binding and repression of key mesoderm genes. More importantly, our study demonstrates the toxicity of dioxin in human embryonic development and uncovered a novel mechanism by which dioxin and AHR regulates lineage commitment. It also illustrates the power of ESC-based models in the systematic study of developmental toxicology.
