Data from: Single cell transcriptomics shows dose-dependent disruption of hepatic zonation by TCDD in mice

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) dose-dependently induces the
development of hepatic fat accumulation and inflammation with fibrosis in
mice initially in the portal region. Conversely, differential gene and
protein expression is first detected in the central region. To further
investigate cell-specific and spatially resolved dose-dependent changes in
gene expression elicited by TCDD, single-nuclei RNA sequencing and spatial
transcriptomics were used for livers of male mice gavaged with TCDD every
4 days for 28 days. The proportion of 11 cell (sub)types across 131,613
nuclei dose-dependently changed with 68% of all portal and central
hepatocyte nuclei in control mice being overtaken by macrophages following
TCDD treatment. We identified 368 (portal fibroblasts) to 1,339
(macrophages) differentially expressed genes. Spatial analyses revealed
initial loss of portal identity that eventually spanned the entire liver
lobule with increasing dose. Induction of R-spondin 3 (Rspo3) and
pericentral Apc, suggested dysregulation of the Wnt/β-catenin signaling
cascade in zonally resolved steatosis. Collectively, the integrated
results suggest disruption of zonation contributes to the pattern of
TCDD-elicited NAFLD pathologies.