Effects of Ionizing Radiation on Proliferation and Differentiation of Mouse Induced Pluripotent Stem Cells

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  • HAYASHI Naoki
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health, Sciences
  • MONZEN Satoru
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health, Sciences
  • ITO Koichi
    Department of Biomedical Sciences, Hirosaki University Graduate School of Health, Sciences
  • FUJIOKA Tsuyoshi
    Cell Engineering Division, RIKEN BioResource Center
  • NAKAMURA Yukio
    Cell Engineering Division, RIKEN BioResource Center
  • KASHIWAKURA Ikuo
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health, Sciences

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The present study aimed to estimate the clonogenic and differentiation potential of induced pluripotent stem (iPS) cells exposed to ionizing radiation. Compared with mouse hematopoietic stem/progenitor cells, iPS cells were less sensitive to radiation. To examine the effect of ionizing radiation on the early differentiation pathway of iPS cells, we assessed embryoid body (EB) formation. Although EB formation was observed at all radiation doses, EB diameter decreased in a radiation dose-dependent manner. At the same time, we analyzed the expression of genes specific to differentiation in the initial iPS cells and cells of EB. The expression of the endoderm marker Afp increased remarkably in cells of EB derived from non-irradiated iPS cells; however, in irradiated cells, this expression significantly decreased in a radiation dose-dependent manner. Further, the expressions of the pluripotent stem cell markers Nanog and Oct-4 and the early mesoderm marker Brachyury significantly decreased. The results of the present study suggest that radiosensitivity with regard to gene expression differs at various stages in the early differentiation pathways of iPS cells that lead to the formation of the 3 germ layers; the sensitivity is the highest in the genes expressed during the differentiation pathways of iPS cells, leading to the formation of the endoderm.

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