Genome-wide transcriptomic response of whole blood to radiation

• Published in: Scientific reports Vol. 15; no. 1; pp. 19840 - 13
• Main Authors: Salah, Ahmed, Wollschläger, Daniel, Callari, Maurizio, Schmidberger, Heinz, Marini, Federico, Zahnreich, Sebastian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.06.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114/2391; 692/53/2423; Biodosimetry; Blood - metabolism; Blood - radiation effects; Blood cells; Blood Cells - metabolism; Blood Cells - radiation effects; DNA damage; DNA Damage - radiation effects; Dose-Response Relationship, Radiation; Gene expression; Gene Expression Profiling; Gene Expression Regulation - radiation effects; Genome, Human; Genomes; Genomic analysis; Humanities and Social Sciences; Humans; Ionizing radiation; Male; multidisciplinary; Radiation; Radiation therapy; Radiotherapy; RNA-seq; Science; Science (multidisciplinary); Signal Transduction - radiation effects; Transcription factors; Transcription Factors - genetics; Transcriptome - radiation effects; Transcriptomes; Transcriptomics; Whole blood; X-Rays; Whole blood; Ionizing radiation; Biodosimetry; RNA-seq; Radiotherapy; Transcriptomics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-04898-1

Blood cells are affected 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 2 h and 6 h. 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 (2 h) and 72, 99, 274, and 607 genes (6 h) were differentially expressed (DEG), compared to 0 Gy. The corresponding number of the inferred transcription factors was 255, 253, 274, and 292 after 2 h and 214, 245, 262, and 279 after 6 h. 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 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 blood system.