Characterizing the Immune Cell Transcriptomic Response To Low-Dose Ionizing Radiation

Abstract

Abstract Low-dose exposure to ionizing radiation is increasingly common in medical, industrial, and public settings worldwide. Previous studies examining the impacts of low-dose radiation (LDR) exposure on genetic material, cellular responses, and health have been inconclusive and conflicting. The National Academy of Science, Engineering and Medicine has outlined that future LDR research should utilize single-cell omics technologies and computational workflows to define the molecular signatures of LDR exposure. In partnership with the Canadian Nuclear Laboratories (CNL), we have used single-cell RNA sequencing (scRNA-seq) to characterize the in-vivo immune cell response to chronic LDR. Mature adult (18 weeks-old) C57BL/6 female mice were whole-body-exposed to 60Co gamma radiation for 7 days, at dose rates of 0.06 mGy/h or 0.6 mGy/h, to achieve cumulative absorbed doses of 10 mGy (n=6) or 100 mGy (n=6), respectively. scRNA-seq of cells isolated immediately post-irradiation identified subtle candidate transcriptomic changes caused by LDR exposure in splenic and bone marrow cell populations. As the first scRNA-seq study of in-vivo LDR exposure, we reveal a more detailed description of the cellular response to LDR exposure than available in the current literature. Therefore, dissemination of these results will advance radiation biology and will be valuable for evaluating Nuclear Safety guidelines. The research is funded by the CANDU Owner's Group and the Mitacs Accelerate program.