Single-cell transcriptomic analysis of mouse liver reveals nonparenchymal cells’ intricate responses to PCB126 exposure

Abstract

AbstractPolychlorinated biphenyls (PCBs) are ubiquitous and representative pollutants that pose great health risks. While cells’ responses to dioxin-like PCBs tend to be studied on a bulk scale, few studies have been made from a single-cell level. Here, by using single-cell RNA sequencing, we depicted a detailed landscape of hepatic nonparenchymal cells’ intricate responses to PCB126 exposure. A total of 13 clusters were identified. Notably, PCB126 exposure resulted in cell-type-specific gene expression profiles and genetic pathways. By analyzing genes related to aryl hydrocarbon receptors, we discovered that PCB126 induced the canonical genomic AhR pathway mainly in endothelial cells. In contrast, other cell types showed little induction. Enrichment pathway analysis indicated that immune cells changed their transcriptional patterns in response to PCB126. ScRNA-seq is a powerful tool to dissect underlying mechanisms of chemical toxicity regarding biological heterogeneity. Taken together, our study not only extends our current understanding of PCB126 toxicity, but also emphasizes the importance ofin vivocell heterogeneity in environmental toxicology.