The Trends in Global Gene Expression in Mouse Embryonic Stem Cells During Spaceflight
The Trends in Global Gene Expression in Mouse Embryonic Stem Cells During Spaceflight
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太空飞行期间小鼠胚胎干细胞整体基因表达的趋势
DOI：
10.3389/fgene.2019.00768
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发表时间：
2019-09-06
影响因子：
3.7
通讯作者：
Hang, Haiying
中科院分区：
文献类型：
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作者：
An, Lili;Li, Yanming;Hang, Haiying
太空中的环境与地面上的环境大不相同。太空飞行会导致宇航员的一些生理变化，如骨质流失和免疫系统失调。这些影响威胁着宇航员的太空任务，了解潜在的细胞和分子机制对于管理太空任务的风险非常重要。空间飞行对哺乳动物细胞的生物学影响，特别是DNA损伤，引起了人们的广泛关注。已知Rad 9（-/-）小鼠胚胎干细胞（mESC）对DNA损伤剂极其敏感。在这项研究中，SJ-10卫星计划的一个项目，我们研究了Rad 9（-/-）mESCs和Rad 9（+/+）（野生型）mESCs在太空中的基因表达谱，重点是对诱导，预防或修复基因组DNA损伤至关重要的基因。我们发现，在野生型和Rad 9（-/-）mESCs中，航天下调的基因比上调的基因更多，表明航天对全球基因表达的抑制作用。相反，Rad 9缺失上调的基因多于下调的基因。值得注意的是，太空飞行主要影响器官发育，并影响mESCs中广泛的细胞功能，而Rad 9缺失主要影响血液系统的发育和功能，特别是免疫细胞的发育，分化和功能。太空中小鼠胚胎干细胞的基因表达模式与其他类型的细胞不同。此外，太空飞行和Rad 9缺失都下调了DNA修复基因，这表明太空飞行可能对胚胎干细胞的基因组产生负面影响，并且当基因组维护机制有缺陷时，这种影响可能会恶化。
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.