Evaluation of dioxin induced transcriptomic responses in a 3D human liver microtissue model

Area of Science:

• Toxicology
• Genomics
• Biotechnology

Background:

• Predicting environmental chemical hepatotoxicity is crucial.
• 3D human liver microtissues offer a promising in vitro model.
• Transcriptional dynamics in these models under dioxin exposure require clarification.

Purpose of the Study:

• To characterize the time-series transcriptional responses of 3D human liver microtissues to 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD) exposure.
• To identify temporal patterns of gene expression modulation and pathway activation.
• To compare findings with existing data for species-specific response elucidation.

Main Methods:

• Utilized time-series transcriptomic analysis over a 14-day period.
• Exposed 3D human liver microtissues to TCDD (31 nM).
• Evaluated gene expression changes and biological pathway modulation at multiple time points.

Main Results:

• Observed stable expression of toxicological and homeostasis genes throughout the culture period.
• Detected a weekly pattern in differentially expressed genes following TCDD exposure.
• Identified induction of cell cycle genes (day 3), metabolic pathways (subsequent days), immune/inflammatory response (day 5), and DNA damage response (day 14).

Conclusions:

• 3D human liver microtissues exhibit distinct temporal transcriptional responses to TCDD.
• The model reveals species-specific differences, notably the DNA damage response, not seen in rodent models.
• This 3D model is valuable for predicting long-term toxic effects of environmental chemicals.