Transcriptional alteration of DNA damage response genes after ionizing radiation exposure in induced pluripotent stem cells

Shimada, Mikio*; Tsukada, Kaima*; Miyake, Tomoko*; Kanzaki, Norie   ; Yanagihara, Hiromi*; Matsumoto, Yoshihisa*

Induced pluripotent stem cells (iPSCs) are generated by transduction of reprogramming transcriptional factors. iPSCs have multipotency to differentiate all organs and expected for the application of regenerative medicine. However, it is reported that cancer risk of iPSCs, because of expression of reprogramming factors increased DNA damage. It is important to analysis DNA damage response of iPSCs to prevent chromosomal abnormality and tumor formation. In this study, we attempted to elucidate the molecular mechanism of maintenance of genome stability in iPSCs. RNA-seq analysis by the next generation sequencer showed increased expression of genome maintenance genes such as DNA repair, cell cycle checkpoint and apoptosis. Interestingly, expression level of these genes was decreased after differentiation to the neural stem cells. Furthermore, colony formation assay showed high sensitivity and apoptosis activity to the IR exposure in iPSCs. These results suggested that instead of DNA repair, increasing of apoptosis activity maintain cell population having accurate genome DNA. These molecular insight have important implication for safety medical application of iPSCs.