Single-Cell Sequencing: An Emerging Tool for Biomarker Development in Nuclear Emergencies and Radiation Oncology

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 cannot provide 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. While single-cell RNA sequencing (scRNA-seq) technology is still emerging in radiation research, it holds significant promise for identifying biomarkers related to radiation exposure and tailoring post-radiation medical care. This review aims to focus on current methods of radiation dosimetry and recently identified biomarkers associated with radiation exposure. Additionally, it addresses the development of NGS techniques in the context of radiation situations, such as cancer treatment and emergency events, with a particular emphasis on single-cell sequencing technology.