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Dataset Details (doi: 10.5061/dryad.547d7wmc5)

Superfund Research Program

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

Accession Number: doi: 10.5061/dryad.547d7wmc5

Link to Dataset:

Repository: Dryad

Data Type(s): Underlying data from publication

Summary: 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 precent 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/ -catenin signaling cascade in zonally resolved steatosis. Collectively, the integrated results suggest disruption of zonation contributes to the pattern of TCDD-elicited NAFLD pathologies.

Publication(s) associated with this dataset:
  • Nault R, Saha S, Bhattacharya S, Sinha S, Maiti T, Zacharewski TR. 2022. Single cell transcriptomics shows dose-dependent disruption of hepatic zonation by TCDD in mice. Toxicol Sci doi:10.1093/toxsci/kfac109 PMID:36222588
Project(s) associated with this dataset:
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