Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems

Area of Science:

• Environmental Science
• Toxicology
• Genomics

Background:

• 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental contaminant.
• TCDD exposure causes diverse toxic effects, modulated by the aryl hydrocarbon receptor (AHR).
• Understanding TCDD-induced transcriptional changes is crucial for AHR research in human health.

Purpose of the Study:

• To compile and standardize transcriptomic datasets related to TCDD exposure.
• To provide a resource for investigating the role of AHR in response to TCDD.
• To facilitate research on the transcriptional effects of ligand-activated AHR.

Main Methods:

• Development of the TCDD.Transcriptomics R package.
• Inclusion of 63 experiments with 377 samples across human, mouse, and rat models.
• Standardization of data using consistent preprocessing and annotation methods.

Main Results:

• The TCDD.Transcriptomics package includes data from diverse species, tissues, and exposure conditions.
• Analysis of 'AHR-core' genes revealed expected induction of Ahrr, Nqo1, and Cyp genes by TCDD.
• Specific induction of Aldh3a1 in rat liver and altered Inmt in liver tissue were observed.

Conclusions:

• A comprehensive assessment of TCDD's transcriptomic effects was previously challenging due to data heterogeneity.
• The TCDD.Transcriptomics package offers a standardized, accessible resource for the scientific community.
• Further research is needed, as core AHR-regulated genes show limited overlap across species and tissues.