How single-cell transcriptomics provides insight on hepatic responses to TCDD

Abstract

The prototypical aryl hydrocarbon receptor (AHR) ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been a valuable model for investigating toxicant-associated fatty liver disease (TAFLD). TCDD induces dose-dependent hepatic lipid accumulation, followed by the development of inflammatory foci and eventual progression to fibrosis in mice. Previously, bulk approaches and in vitro examination of different cell types were relied upon to study the mechanisms underlying TCDD-induced liver pathologies. However, the advent of single-cell transcriptomic technologies, such as single-nuclei RNA sequencing (snRNAseq) and spatial transcriptomics (STx), has provided new insights into the responses of hepatic cell types to TCDD exposure. This review explores the application of these single-cell transcriptomic technologies and highlights their contributions towards unraveling the cell-specific mechanisms mediating the hepatic responses to TCDD.