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

JangKeun Kim(Cornell University), Braden Tierney(Cornell University), Eliah Overbey(Cornell University), Ezequiel Dantas(Cornell University), Matías Fuentealba(Buck Institute for Research on Aging), Jiwoon Park(Cornell University), S Narayanan(Florida State University), Fei Wu(Buck Institute for Research on Aging), Deena Najjar(Cornell University), Christopher R. Chin(Cornell University), Cem Meydan(Cornell University), Conor Loy(Cornell University), Begüm Aydoğan Mathyk(University of South Florida), Rémi Klotz(University of Southern California), Veronica Ortiz(University of Southern California), Khiem Nguyen(Buck Institute for Research on Aging), Krista Ryon(Cornell University), Namita Damle(Cornell University), Nadia Houerbi(Cornell University), Laura Pătraș(Cornell University), Nathan Schanzer(New York Medical College), Gwyneth A. Hutchinson(University of California, San Francisco), Jonathan Foox(Cornell University), Chandrima Bhattacharya(Cornell University), Matthew MacKay(Cornell University), Evan E. Afshin(Cornell University), Jeremy Wain Hirschberg(Cornell University), Ashley S. Kleinman(Cornell University), Julian C. Schmidt, Caleb M. Schmidt(Colorado State University), Michael A. Schmidt, Afshin Beheshti(Broad Institute), Irina Matei(Cornell University), David Lyden(Cornell University), Sean Mullane(SpaceX (United States)), Amran K. Asadi(SpaceX (United States)), Joan Sesing Lenz(Cornell University), Omary Mzava(Cornell University), Min Yu(University of Southern California), Saravanan Ganesan(Cornell University), Iwijn De Vlaminck(Cornell University), Ari Melnick(Cornell University), Darko Barišić(Cornell University), Daniel A. Winer(University of Southern California), Sara R. Zwart(The University of Texas Medical Branch at Galveston), Brian Crucian(Johnson Space Center), Scott M. Smith(Johnson Space Center), Jaime Mateus(Ames Research Center), David Furman(Buck Institute for Research on Aging), Christopher E. Mason(Cornell University)
Nature Communications
June 11, 2024
10.1038/s41467-024-49211-2
Cited by 55Open Access
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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.

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