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

Area of Science:

• Space biology and astrobiology
• Molecular biology and genetics
• Cellular biology

Background:

• Spaceflight induces physiological changes in astronauts, including bone loss and immune dysregulation.
• Understanding spaceflight's biological effects on mammalian cells, particularly DNA damage, is crucial for mission safety.
• Rad9-deficient mouse embryonic stem cells (mESCs) are highly sensitive to DNA damage agents.

Purpose of the Study:

• To investigate the gene expression profiles of wild-type and Rad9-deficient mESCs under spaceflight conditions.
• To identify genes involved in DNA damage response, induction, prevention, and repair affected by spaceflight.
• To understand the distinct effects of spaceflight and Rad9 deficiency on mESC gene expression.

Main Methods:

• Comparison of gene expression profiles between Rad9-/- mESCs and Rad9+/+ (wild-type) mESCs exposed to spaceflight.
• Analysis focused on genes critical for genomic DNA lesion management.
• Utilized data from the SJ-10 satellite program for spaceflight experiments.

Main Results:

• Spaceflight downregulated more genes than upregulated in both wild-type and Rad9-/- mESCs, indicating a global gene expression suppression.
• Rad9 deletion upregulated more genes than downregulated, contrasting with spaceflight's suppressive effect.
• Spaceflight primarily impacted organ development and cellular functions, while Rad9 deletion affected hematological and immune cell systems.

Conclusions:

• Spaceflight exhibits a suppressive effect on global gene expression in mESCs, with distinct patterns compared to other cell types.
• Both spaceflight and Rad9 deletion downregulated DNA repair genes, suggesting potential negative impacts on embryonic stem cell genomes.
• The detrimental effects of spaceflight on genome integrity may be exacerbated in cells with defective DNA repair mechanisms, like Rad9-/- mESCs.