Evaluation of developmental toxicant identification using gene expression profiling in embryonic stem cell...

Area of Science:

• Toxicology
• Developmental Biology
• Genomics

Background:

• The murine embryonic stem cell test (EST) is an alternative method for assessing chemical developmental toxicity.
• Integrating transcriptomics into the EST can enhance prediction accuracy and define its applicability domain.

Purpose of the Study:

• To evaluate the efficacy of transcriptomics in the EST for identifying developmental toxicants.
• To assess two specific gene sets for predicting developmental toxicity.

Main Methods:

• Utilized transcriptomics analysis on embryonic stem cells (ESCs) exposed to 12 known developmental toxicants.
• Applied principal component analysis on predefined gene sets to define a "differentiation track" representing ESC differentiation.
• Evaluated compound-induced deviations from the differentiation track to predict toxicity.

Main Results:

• Successfully predicted developmental toxicity for 83% and 67% of compounds using the "Van_Dartel_heartdiff_24h" and "EST biomarker genes" sets, respectively.
• Transcriptomics analysis identified compound-induced changes in gene expression related to ESC differentiation.

Conclusions:

• Transcriptomics application in the EST shows promise for improving the prediction of chemical developmental toxicity.
• This approach may enhance the overall applicability and reliability of the EST for toxicological assessments.