Single-Cell Sequencing: An Emerging Tool for Biomarker Development in the Event of Nuclear Emergency

Next-generation sequencing (NGS) has been well applied to assess genetic abnormalities in various biological samples to investigate disease mechanisms. With the advent of high-throughput and automatic testing platforms, NGS can identify radiation-sensitive and dose-responsive biomarkers, contributing to triage patients and determining risk groups for treatment in a nuclear emergency. While bulk NGS provides a snapshot of the average gene expression or genomic changes within a group of cells after the radiation, it does not give information on individual cells within the population. On the other hand, single-cell sequencing involves isolating individual cells and sequencing the genetic material from each cell separately. This approach allows for the identification of gene expression and genomic changes in individual cells, providing a high-resolution view of cellular diversity and heterogeneity within a sample. Single-cell sequencing is particularly useful to identify cell-specific features of dose-response and organ-response genes. Although single-cell RNA sequencing (scRNA-seq) technology is still in its infancy in radiation research, it has great potential for identifying biomarkers associated with radiation exposure and for personalized post-radiation medical care. The aim of this review is to focus on current dosimetry methods, recently identified radiation-induced biomarkers, as well as the application of NGS techniques in facing a nuclear accident, specifically the single-cell sequencing technology.