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The liver is the primary site of metabolism of drugs and xenobiotic compounds, and exhibits remarkably intricate spatiotemporal regulation of gene expression and biological function. Disruption of the underlying regulatory mechanisms can contribute to the development of pathological states such as non-alcoholic fatty liver disease and liver fibrosis. Here we use previously generated single cell transcriptomic data to examine the disruption of rhythmic and zonal gene expression patterns in the mammalian liver lobule caused by exposure to the potent environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While both rhythmicity and zonation of gene expression are perturbed, the suppressive effect of TCDD on rhythmicity is stronger. We propose a likely mechanism of these disruptive effects of TCDD mediated by the Aryl hydrocarbon Receptor (AhR). Our work provides a framework for computational query and modeling of the disruption of hepatic function by chemical pollutants. |