Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration
- 544 Downloads
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.
KeywordsPrecision toxicology Single cell sequencing Phenotype focusing Cell isolation
This work was supported by the National Special Program of Transgenic Research (Grant No. 2016ZX08011-005). The authors thank Beijing Advanced Innovation Center for Food Nutrition and Human Health for their kind support of this work.
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest.
- Doherty M, Metcalfe T, Guardino E, Peters E, Ramage L (2016) Precision medicine and oncology: an overview of the opportunities presented by next-generation sequencing and big data and the challenges posed to conventional drug development and regulatory approval pathways. Ann Oncol 27(8):1644–1646. doi: 10.1093/annonc/mdw165 CrossRefPubMedGoogle Scholar
- Lauschke VM, Hendriks DFG, Bell CC, Andersson TB, Ingelman-Sundberg M (2016) Novel 3D Culture systems for studies of human liver function and assessments of the hepatotoxicity of drugs and drug candidates. Chem Res Toxicol 29(12):1936–1955. doi: 10.1021/acs.chemrestox.6b00150 CrossRefPubMedGoogle Scholar
- Plummer S, Sharpe RM, Hallmark N, Mahood IK, Elcombe C (2007) Time-dependent and compartment-specific effects of in utero exposure to di(n-butyl) phthalate on gene/protein expression in the fetal rat testis as revealed by transcription profiling and laser capture microdissection. Toxicol Sci 97(2):520–532. doi: 10.1093/toxsci/kfm062 CrossRefPubMedGoogle Scholar
- Schillebeeckx M, Schrade A, Lobs AK, Pihlajoki M, Wilson DB, Mitra RD (2013) Laser capture microdissection-reduced representation bisulfite sequencing (LCM-RRBS) maps changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse. Nucleic Acids Res 41(11):e116. doi: 10.1093/nar/gkt230 CrossRefPubMedPubMedCentralGoogle Scholar