Effects of Ionizing Radiation on Proliferation and Differentiation of Mouse Induced Pluripotent Stem Cells
Effects of Ionizing Radiation on Proliferation and Differentiation of Mouse Induced Pluripotent Stem Cells
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DOI：
10.1269/jrr.11138
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发表时间：
2012-03-01
影响因子：
2
通讯作者：
Kashiwakura, Ikuo
中科院分区：
文献类型：
--
作者：
Hayashi, Naoki;Monzen, Satoru;Kashiwakura, Ikuo
本研究旨在评估电离辐射下诱导多能干细胞（iPS）的克隆和分化潜能。与小鼠造血干细胞/祖细胞相比，iPS细胞对辐射的敏感性较低。为了研究电离辐射对诱导多能干细胞早期分化途径的影响，我们评估了胚状体（EB）的形成。尽管在所有辐射剂量下均观察到EB形成，但EB直径呈辐射剂量依赖性下降。同时，我们分析了分化特异性基因在初始iPS细胞和EB细胞中的表达。未辐照诱导多能干细胞衍生的EB细胞中内胚层标志物Afp的表达显著增加；然而，在辐照细胞中，这种表达以辐射剂量依赖的方式显著降低。多能干细胞标记物Nanog、Oct-4和早期中胚层标记物Bmchyury的表达显著降低。本研究结果表明，在诱导多能干细胞形成3胚层的早期分化途径的不同阶段，基因表达的种族敏感性是不同的；在诱导多能干细胞分化过程中表达的导致内胚层形成的基因敏感性最高。
The present study aimed to estimate the clonogenic and differentiation potential of induced pluripotent stern (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 Bmchyury significantly decreased. The results of the present study suggest that racliosensitivity 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.