(A) Summary of cell types detected in liver and their overall functions. (B) Experimental design and data analysis. From postnatal days (PND) 2 to 4, male C57BL/6 mouse pups were supralingually exposed to BDE-99 (57 mg/kg) or corn oil (10 ml/kg) as the vehicle control. Livers were removed at 15 months of age for scRNA-Seq (n = 3 per group). The shift in expression in drug processing signatures, cell-cell communication patterns, and immunological markers were investigated in each cell type. For mechanistic investigations of the gut-liver axis in mediating PBDE hepatotoxicity, we compared the hepatic transcriptomic signatures to our recently published dataset on gut microbiome in adult male C57BL/6 mice that were developmentally exposed to BDE-99 or vehicle using the same dosing regimen. Furthermore, the necessity of the gut microbiome in maintaining basal hepatic immune tolerance is validated using scRNA-seq conducted in livers of adult conventional and germ-free mice.