RBIO-06. Transcriptomic change of human induced pluripotent stem cells (iPSCs)-derived neuronal cells after particle beam irradiation

Abstract Particle radiation therapy is now widely used for the treatment of brain tumors, because it can precisely prescribe the maximum radiation dose to the tumor and minimize radiation exposure of surrounding normal brain. Recent studies on risk of cognitive decline after proton therapy reported optimistic results, however the damage and effect to the neuronal cells or blood brain barrier is still largely unknown. In this study, we irradiated particle ion beam such as proton, carbon and helium to the neural cells derived from human induced pluripotent stem cells (iPSCs). Twenty-four hours after 1, 2, 5 and 10 Gy irradiation, annexin v, which indicates early apoptosis, positive cells did not increase and propidium iodide which is the marker of late apoptosis or necrosis, increased to 8.3 % only in the 10 Gy- helium irradiated neuron. Transcriptomic analysis using RNA-seq was performed with samples 24 hours after 5 Gy irradiation. In proton beam irradiated neurons, the number of up- or down- regulated genes (fold change >=2 and p<0.05) was 108 and 128. From genetic ontology (GO) analysis, ATP binding, adenyl nucleotide binding, and adenyl ribonucleotide binding, were differentially expressed in molecular function (MF). In carbon beam irradiated neurons, the number of up- or down- regulated genes was 75 and 85. From GO analysis, in biological process (BP), intrinsic apoptotic signaling pathway by p53, arachidonic acid metabolite production, leukotriene production, were up-regulated and in cellular component (CC), nucleosome, DNA packing complex and protein-DNA complex, were up-regulated. While, in BP, cell migration, cell cycle, signal transduction in response to DNA damage and DNA damage check point were down-regulated. These findings suggested that high linear energy transfer radiation, carbon ion beam could cause more severe DNA damage in neurons compared with proton, therefore, lead apoptosis and inflammation after cell cycle arrest and DNA damage checkpoint.