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Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism
Boyang Zhang1,2, Kunlun Huang1,2, Liye Zhu1,2
1Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Tsinghua East Road, Beijing, 100083, China.
Abstract:
In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.
Insights
Precision toxicology uses single-cell sequencing to analyze toxicity mechanisms. This approach enhances detection of subtle cellular changes, aiding in mitigating health threats from chemical and drug exposure.
Area of Science:
- Toxicology
- Molecular Biology
- Genomics
Background:
- Chemical and drug toxicity pose significant threats to human health.
- Understanding the precise mechanisms of toxicity is crucial for developing effective countermeasures.
- Current methods may lack the sensitivity to detect subtle, early-stage cellular changes.
Purpose of the Study:
- Introduce the novel concept of precision toxicology.
- Highlight the application of single-cell sequencing for investigating toxicity.
- Demonstrate the potential for improved detection and mitigation of toxicological effects.
Main Methods:
- Utilizing single-cell isolation techniques such as laser capture microdissection (in vivo) and flow cytometric sorting (in vitro).
- Performing single-cell sequencing-based analysis to investigate cellular responses.
- Analyzing subtle intracellular changes in response to exogenous substances.
Main Results:
- Precision toxicology enables sensitive and specific investigation of toxicity modes of action.
- The approach allows for the detection of subtle intracellular alterations.
- Identified single-cell isolation and sequencing as key components for future toxicological studies.
Conclusions:
- Precision toxicology offers a powerful new paradigm for understanding and addressing chemical and drug toxicity.
- Single-cell sequencing techniques are poised to become a significant trend in toxicological research and evaluation.
- This approach can lead to better strategies for controlling and alleviating adverse health effects.
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