ArticleToxicological sciences : an official journal of the Society of Toxicology2023
Single-cell transcriptomics shows dose-dependent disruption of hepatic zonation by TCDD in mice.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Zonal hepatocellular responses to acute ethanol consumption: impacts on mitochondrial function and liver metabolism.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Mapping safety in space: the emerging role of spatial transcriptomics in safe drug development.Frontiers in toxicology · 2026Review
- Cell type- and species-specific regulation of hepatic lncRNAs by TCDD-activated aryl hydrocarbon receptor.Scientific reports · 2025Article
- Shift in the urinary metabolome associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin activation of the hepatic aryl hydrocarbon receptor.Scientific reports · 2025Article
- The Aryl Hydrocarbon Receptor in Neurotoxicity: An Intermediator Between Dioxins and Neurons in the Brain.Toxics · 2025Review
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Review
- Progress in toxicogenomics to protect human health.Nature reviews. Genetics · 2025Review
- Spatial-Omics Methods and Applications.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Mass Spectrometry Imaging for Spatial Toxicology Research.Journal of mass spectrometry : JMS · 2024Review
- MitoTracker Red for isolation of zone-specific hepatocytes and characterization of hepatic sublobular metabolism.Biochemical and biophysical research communications · 2024Article
- Unique challenges and best practices for single cell transcriptomic analysis in toxicology.Current opinion in toxicology · 2024Article
- Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension.iScience · 2024Article
- Spatial Transcriptomics: A Powerful Tool in Disease Understanding and Drug Discovery.Theranostics · 2024Review
- How single-cell transcriptomics provides insight on hepatic responses to TCDD.Current opinion in toxicology · 2023Article
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.Toxicology and applied pharmacology · 2023Article
- The Ah Receptor from Toxicity to Therapeutics: Report from the 5th AHR Meeting at Penn State University, USA, June 2022.International journal of molecular sciences · 2023Article
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
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 1339 (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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.