Genome-wide transcriptomic response of whole blood to radiation

The hematological system is impacted in nearly all ionizing radiation exposure scenarios. Whole transcriptome data offer detailed insights into blood’s radiation response, crucial for radiotherapy and biodosimetry. We conducted genome-wide RNA-seq analysis on blood from three donors irradiated ex vivo with X-rays and incubated for 2h and 6h. Gene expression was subject to strong inter-donor variation and time post-exposure. After 0.5, 1, 2, and 4 Gy X-rays, 5, 33, 84, and 364 genes (2h) and 72, 99, 274, and 607 genes (6h) were differentially expressed (DEG), compared to 0 Gy. The corresponding number of the inferred transcription factors was 255, 253, 274, and 292 after 2h and 214, 245, 262, and 279 after 6h. In sham-irradiated blood, 924 DEGs and 165 transcription factors were affected by ex vivo incubation alone. We identified 34 radioresponsive DEGs not previously described, 8 and 9 showing significant positive or negative correlations with dose, respectively, including GPN1, MRM2, G0S2, and PTPRS. DNA damage signaling pathways were affected from the lowest dose, with doses ≥ 2 Gy additionally triggering proinflammatory responses. This first genome-wide RNA-seq study of ex vivo X-ray-exposed human blood reveals novel radiosensitive genes, transcription factors, and pathways, enhancing the understanding of the consequences of diagnostic, therapeutic, or accidental exposures on the highly radioresponsive hematological system.