Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan.
Radiation Institute for Science and Engineering, Prairie View A&M University, Prairie View, TX 77446, USA.
Int J Mol Sci. 2024 Mar 14;25(6):3283. doi: 10.3390/ijms25063283.
As a space project, in "Stem Cells" by the Japan Aerospace Exploration Agency (JAXA), frozen mouse ES cells were stored on the International Space Station (ISS) in the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) for 1584 days. After taking these cells back to the ground, the cells were thawed and cultured, and their gene expressions were comprehensively analyzed using RNA sequencing in order to elucidate the early response of the cells to long-time exposure to space radiation consisting of various ionized particles. The comparisons of gene expression involved in double-stranded break (DSB) repair were examined. The expressions of most of the genes that were involved in homologous recombination (HR) and non-homologous end joining (NHEJ) were not significantly changed between the ISS-stocked cells and ground-stocked control cells. However, the transcription of Trp53inp1 (tumor protein 53 induced nuclear protein-1), Cdkn1a (p21), and Mdm2 genes increased in ISS-stocked cells as well as Fe ion-irradiated cells compared to control cells. This suggests that accumulated DNA damage caused by space radiation exposure would activate these genes, which are involved in cell cycle arrest for repair and apoptosis in a p53-dependent or -independent manner, in order to prevent cells with damaged genomes from proliferating and forming tumors.
作为一项太空计划,在日本宇宙航空研究开发机构(JAXA)的“干细胞”项目中,冷冻的小鼠胚胎干细胞被储存在国际空间站(ISS)的零下 80 度实验室冷冻器(MELFI)中长达 1584 天。将这些细胞带回地面后,对其进行解冻和培养,并使用 RNA 测序全面分析其基因表达情况,以阐明细胞对由各种离子化粒子组成的长时间太空辐射的早期反应。研究比较了与双链断裂(DSB)修复相关的基因表达。参与同源重组(HR)和非同源末端连接(NHEJ)的大多数基因的表达在 ISS 储存细胞和地面储存对照细胞之间没有明显变化。然而,与对照细胞相比,ISS 储存细胞和 Fe 离子辐照细胞中转录的 Trp53inp1(肿瘤蛋白 53 诱导核蛋白-1)、Cdkn1a(p21)和 Mdm2 基因增加。这表明,由太空辐射暴露引起的累积 DNA 损伤会激活这些基因,这些基因参与细胞周期阻滞修复和细胞凋亡,无论是依赖 p53 还是非依赖 p53 的方式,以防止基因组受损的细胞增殖并形成肿瘤。