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Shimada, Mikio*; Tokumiya, Takumi*; Miyake, Tomoko*; Tsukada, Kaima*; Kanzaki, Norie; Yanagihara, Hiromi*; Kobayashi, Junya*; Matsumoto, Yoshihisa*
Journal of Radiation Research (Internet), 64(2), p.345 - 351, 2023/03
Times Cited Count：1 Percentile：0.01(Biology)Kanzaki, Norie; Shimada, Mikio*; Yanagihara, Hiromi*
no journal, ,
After ionizing radiation exposure, several types of DNA damage occur in mammalian cells. Several studies have been reported that the mutation type depends on the radiation type and the cell type. Thus, it is important to characterize the type of mutation caused by irradiation for understanding of the biological effects of radiation. This study is a foundational investigation of construction of data analysis method dedicated to characteristics extraction of mutations. Two datasets were hypothetically made by reference to previous researches. The data was composed of eight items, namely two types of transition, four types of transversion, insertion, and deletion. The datasets were first analyzed by Self-Organizing Maps. We categorized and predicted the characteristics of mutations. This result was compared with those of other multivariate analysis methods. The data with similar mutation patterns was closely located on the output map, indicating the variation of mutations given by different radiation types.
Shimada, Mikio*; Tsukada, Kaima*; Miyake, Tomoko*; Kanzaki, Norie; Yanagihara, Hiromi*; Matsumoto, Yoshihisa*
no journal, ,
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.
Shimada, Mikio*; Kanzaki, Norie; Yanagihara, Hiromi*; Miyake, Tomoko*; Matsumoto, Yoshihisa*
no journal, ,
Although mutation frequency depends on organ cell types and differentiation level, it is not fully understood that organ cell types dependent mutation frequency in human cells. In this study, we aimed to establish measurement system of radiation dependent mutation frequency for analyze radiation effect to the human body. For this purpose, we derived four different organ cells such as neural cells, skin keratinocytes, heart muscle cells and blood cells from hiPSCs. Further, using artificial intelligence technology and machine leaning method, we w analyzed differences of mutation frequency during samples.
