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A Manual Small Molecule Screen Approaching High-throughput Using Zebrafish Embryos
Published on: November 8, 2014
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Zebrafish cell lines and high-throughput transcriptomics: advancing in vitro and bioinformatics methods for
Peter G Schumann1, Joseph Bundy2, Derik E Haggard2
1Office of Research and Development, Center for Computational Toxicology and Exposure, Great Lakes Toxicology and Ecology Division, U.S. Environmental Protection Agency, Duluth, MN 55804, United States.
Toxicological Sciences : an Official Journal of the Society of Toxicology
|September 19, 2025
Summary
Zebrafish cell lines show promise for high-throughput screening of chemical toxicity, offering a more ecologically relevant alternative to mammalian models. This approach aids in prioritizing chemicals for environmental risk assessment.
Area of Science:
- Environmental Toxicology
- In Vitro Toxicology
- High-Throughput Screening
Background:
- Traditional animal testing for chemical toxicity is insufficient for current risk assessment needs.
- Existing in vitro methods often use mammalian cell lines, limiting their applicability to environmental species.
- New Approach Methodologies (NAMs) like transcriptomics are needed for efficient chemical prioritization.
Purpose of the Study:
- To assess the utility of zebrafish cell lines in high-throughput transcriptomics for environmental risk assessment.
- To determine if transcriptomic data from zebrafish cells can predict aquatic toxicity endpoints.
- To evaluate the ecological relevance of in vitro transcriptomics using zebrafish models.
Main Methods:
- Screening of 42 chemicals in two zebrafish cell lines (ZFL and ZEM2S) using the TempO-Seq platform.
- Derivation of transcriptomic points-of-departure (tPODs) via gene-level analysis and pathway-based approaches.
- Application of in vitro-in vivo extrapolation (IVIVE) models and cross-species extrapolation tools.
Main Results:
- tPODs derived from zebrafish cells, when extrapolated, were generally protective of aquatic in vivo endpoints.
- Differential gene expression analysis revealed cell-type-specific chemical effects, emphasizing the need for multiple cell lines.
- Pathway analysis and cross-species tools facilitated extrapolation of chemical effects, enhancing ecological relevance.
Conclusions:
- Zebrafish cell lines can generate biologically meaningful data for high-throughput transcriptomics pipelines.
- This methodology supports environmental risk assessment by providing ecologically relevant chemical toxicity data.
- Integrating multiple cell types and cross-species tools improves the predictive power and relevance of in vitro toxicity testing.
