Spaceflight alters molecular networks linked to diverse human diseases in a single cellular model

The International Space Station provides an opportunity to study the impact of spaceflight on gene expression and possible links to human health. Our study investigates global changes in messenger RNA (mRNA) abundance in the THP-1 cell line, a monocyte-macrophage lineage known for plasticity and immune reprogramming features. We identified pathways positively enriched with genes affecting muscle and cardiac contraction, neuronal system, and sensory perception. Available computational models identified links with health issues, including cardiac, neurological, muscular, and renal disorders and alterations in senses. Specific mechanistic networks were identified: retinoid metabolism, cAMP (adenosine 3',5'-monophosphate)/CREB (cAMP response element-binding protein) signaling, and glutamatergic receptor signaling, which were associated with changes in vision, sleep, and movement, respectively. A considerable reduction is observed in E2F-regulated transcription of G₂-M and DNA repair genes. A c-myc-regulated mRNA splicing pathway was identified and found commonly down-regulated in other mission datasets. Our results offer a stimulating framework for several health states encountered during spaceflight and can be further used as an accelerated disease and drug discovery model.