Genomics, Proteomics, Bioinformatics

Sequencing The Inspiration 4 Crew’s Genomic Responses To Spaceflight

By Keith Cowing
Status Report
Nature via Pub Med
March 18, 2025
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Sequencing The Inspiration 4 Crew’s Genomic Responses To Spaceflight
Log2 fold change heatmap of the “spaceflight signatures in mice” in 27 datasets with 10 different mouse tissues. Age (Day). Duration (Day). 1,288 up-regulated and 896 down-regulated genes. — Nature via Pub Med

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew.

We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a “spaceflight signature” of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways.

We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes.

Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts.

In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

Astrobiology

Explorers Club Fellow, ex-NASA Space Station Payload manager/space biologist, Away Teams, Journalist, Lapsed climber, Synaesthete, Na’Vi-Jedi-Freman-Buddhist-mix, ASL, Devon Island and Everest Base Camp veteran, (he/him) 🖖🏻