空间辐射对基因组的作用及机理研究

Space radiation and microgravity are the two important features of space environment. Radiation can damage the cellular genomic DNA. The combined effects of space environment especially space radiation and microgravity on the cellular genomic DNA remains unclear. This research has important theoretical and practical value. People can obtain relative information through real space experiments and simulated experiments on the ground. Each approach has its advantages and disadvantages. It is ideal to combine these two approaches together. However, such report is rare. In our previous work, we performed the experiments on board the recoverable microgravity satellite SJ-10. Using the wild type and corresponding radiation sensitive mutant mammalian cells as the models, we have obtained their RNA and DNA deep sequencing results after the flight. In this study, we will do the simulated experiments and the in-depth study of the mechanisms based on the experimental parameters and the experimental data obtained from the real space experiment. It is expected to get the regular pattern of the effects of space radiation on genomic stability and gene expression profile. It is also aimed to discover novel sensitive biological molecules as space radiation biomarkers, which will be useful for developing sensitive detecting methods of the biological effects of space radiation in the future.

空间辐射和微重力是空间环境的两个重要特点。辐射最重要的靶分子之一是细胞遗传物质基因组DNA。空间环境特别是空间辐射和微重力对基因组的复合作用目前还不清楚，这一研究具有重要理论和应用价值。空间实验和地面模拟实验是人们进行这方面研究的两条途径，各有其优缺点。目前针对空间实验数据，结合地面模拟实验进行深入的空间环境对基因组作用及机理研究的研究很少见到。申请者前期在实践十号返回式科学卫星上进行了实验，获得了DNA损伤敏感的缺陷型小鼠胚胎干细胞和对照野生小鼠胚胎干细胞空间飞行后的RNA及DNA深度测序结果。本项目，我们将在前期获得的空间实验参数和实验数据基础上，进行相应的地面模拟实验和深入的机理研究，获得空间辐射对基因组稳定性改变和基因表达谱改变的影响规律；寻找新的空间辐射敏感标志生物分子，并进行功能验证，为将来开发更灵敏的空间辐射生物学效应检测方法奠定基础。

空间辐射和微重力是空间环境的两个重要特点。辐射最重要的靶分子之一是细胞遗传物质基因组DNA。空间环境特别是空间辐射和微重力对基因组的复合作用目前还不清楚，这一研究具有重要理论和应用价值。我们前期在SJ-10号返回式科学卫星上进行了实验，获得了DNA损伤敏感的缺陷型小鼠胚胎干细胞和对照野生小鼠胚胎干细胞空间飞行后的RNA及DNA深度测序结果。本项目中，我们对测序结果进行了深入分析，发现空间飞行造成了在Rad9+/+ mESCs和Rad9-/- mESCs中下调的基因数都多于上调的基因数，这表明空间飞行对全基因表达具有抑制作用。相反，Rad9缺失导致更多的上调基因。空间飞行mESCs和地面mESCs之间进行差异表达基因（DEGs）比较，Rad9-/- mESCs和Rad9+/+ mESCs之间也进行DEGs比较，结果发现比较出的DEGs非常不同。而且，小鼠胚胎干细胞在空间中的基因表达模式不同于其他类型的细胞。此外，空间飞行和Rad9缺失都下调了DNA修复基因，这表明空间飞行对胚胎干细胞的基因组有负面影响，并且当基因组维持机制存在缺陷时，这种负面影响可能变得更加严重。由此提示，在挑选宇航员和太空旅行者时应当排除基因组维护系统有缺陷（如DNA损伤修复或细胞周期监控基因有缺陷的）的人员。