The Trends in Global Gene Expression in Mouse Embryonic Stem Cells During Spaceflight

The environment in space differs greatly from the environment on the ground. Spaceflight causes a number of physiological changes in astronauts, such as bone loss and immune system dysregulation. These effects threaten astronauts’ space missions, and understanding the underlying cellular and molecular mechanisms is important to manage the risks of space missions. The biological effects of spaceflight on mammalian cells, especially with regards to DNA damage, have attracted much attention. Rad9 −/− mouse embryonic stem cells (mESCs) are known to be extremely sensitive to DNA damage agents. In this study, a project of the SJ-10 satellite programme, we investigated the gene expression profiles of both Rad9 −/− mESCs and Rad9 +/+ (wild-type) mESCs in space with a focus on genes critical for inducing, preventing, or repairing genomic DNA lesions. We found that spaceflight downregulated more genes than it upregulated in both wild-type and Rad9 −/− mESCs, indicating a suppressive effect of spaceflight on global gene expression. In contrast, Rad9 deletion upregulated more genes than it downregulated. Of note, spaceflight mainly affected organ development and influenced a wide range of cellular functions in mESCs, while Rad9 deletion mainly affected the development and function of the hematological system, especially the development, differentiation and function of immune cells. The patterns of gene expression in mouse embryonic stem cells in space is distinct from those in other types of cells. In addition, both spaceflight and Rad9 deletion downregulated DNA repair genes, suggesting a possibility that spaceflight has negative effects on genome for embryonic stem cells and the effects are likely worsen when the genome maintenance mechanism is defective.

太空环境与地面环境存在显著差异。航天飞行可导致宇航员出现多种生理变化，例如骨质流失、免疫系统功能失调。此类效应会对宇航员的太空任务构成威胁，因此解析其背后的细胞与分子机制，对于管控太空任务风险具有重要意义。航天飞行对哺乳动物细胞的生物学效应，尤其是在DNA损伤相关领域，已引发广泛关注。研究表明，Rad9基因缺失（Rad9 -/-）的小鼠胚胎干细胞（mouse embryonic stem cells, mESCs）对DNA损伤剂具有极高的敏感性。本研究作为SJ-10卫星计划的项目之一，探究了太空环境下Rad9 -/- mESCs与Rad9 +/+（野生型）mESCs的基因表达谱，重点关注参与诱导、预防或修复基因组DNA损伤的关键基因。研究结果显示，在野生型与Rad9 -/- mESCs中，航天飞行诱导下调的基因数量均多于上调基因，表明航天飞行对全局基因表达存在抑制作用。与之形成对比的是，Rad9基因缺失所上调的基因数量多于下调基因。值得注意的是，航天飞行主要影响器官发育，并对小鼠胚胎干细胞的多种细胞功能产生广泛影响；而Rad9基因缺失主要影响造血系统的发育与功能，尤其是免疫细胞的发育、分化及功能。太空环境中小鼠胚胎干细胞的基因表达模式与其他类型细胞存在显著区别。此外，航天飞行与Rad9基因缺失均下调了DNA修复相关基因，这提示航天飞行可能对胚胎干细胞的基因组产生负面影响，且当基因组维持机制存在缺陷时，此类效应或进一步加剧。