Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight

• DOI: 10.1038/s41467-024-49211-2
• Publication Date: 2024-06-11T16:03:56Z
• Authors: JangKeun Kim; Braden T. Tierney; Eliah G. Overbey; Ezequiel Dantas; Matias Fuentealba; Jiwoon Park; S. Anand Narayanan; Fei Wu; Deena Najjar; Christopher R. Chin; Cem Meydan; Conor Loy; Begum Mathyk; Remi Klotz; Veronica Ortiz; Khiem Nguyen; Krista A. Ryon; Namita Damle; Nadia Houerbi; Laura I. Patras; Nathan Schanzer; Gwyneth A. Hutchi...; Jonathan Foox; Chandrima Bhattac...; Matthew Mackay; Evan E. Afshin; Jeremy Wain Hirsc...; Ashley S. Kleinman; Julian C. Schmidt; Caleb M. Schmidt; Michael A. Schmidt; Afshin Beheshti; Irina Matei; David Lyden; Sean Mullane; Amran Asadi; Joan S. Lenz; Omary Mzava; Min Yu; Saravanan Ganesan; Iwijn De Vlaminck; Ari M. Melnick; Darko Barisic; Daniel A. Winer; Sara R. Zwart; Brian E. Crucian; Scott M. Smith; Jaime Mateus; David Furman; Christopher E. Mason
• Keywords: Spaceflight; Cell type; Human spaceflight

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, muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, identified a "spaceflight signature" of gene expression characterized by enrichment oxidative phosphorylation, UV response, function, TCF21 pathways. confirmed presence signature independent datasets, including NASA Twins Study, skin spatial transcriptomics, 817 GeneLab mouse transcriptomes. Finally, observed (1) T cells showed up-regulation FOXP3, (2) MHC class I genes exhibited long-term suppression, (3) infection-related pathways were associated with microbiome shifts. summary, study reveals conserved distinct disruptions occurring details roadmap potential countermeasures preserve astronaut health.