Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight
JangKeun Kim, Braden Tierney, Eliah Overbey, Ezequiel Dantas, Matías Fuentealba, Jiwoon Park, S Narayanan, Fei Wu, Deena Najjar, Christopher R. Chin, Cem Meydan, Conor Loy, Begüm Aydoğan Mathyk, Rémi Klotz, Veronica Ortiz, Khiem Nguyen, Krista Ryon, Namita Damle, Nadia Houerbi, Laura Pătraș, Nathan Schanzer, Gwyneth A. Hutchinson, Jonathan Foox, Chandrima Bhattacharya, Matthew MacKay, Evan E. Afshin, Jeremy Wain Hirschberg, Ashley S. Kleinman, Julian C. Schmidt, Caleb M. Schmidt, Michael A. Schmidt, Afshin Beheshti, Irina Matei, David Lyden, Sean Mullane, Amran K. Asadi, Joan Sesing Lenz, Omary Mzava, Min Yu, Saravanan Ganesan, Iwijn De Vlaminck, Ari Melnick, Darko Barišić, Daniel A. Winer, Sara R. Zwart, Brian Crucian, Scott M. Smith, Jaime Mateus, David Furman, Christopher E. Mason
Abstract
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.