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

Author:

Kim JangKeunORCID,Tierney Braden T.ORCID,Overbey Eliah G.ORCID,Dantas EzequielORCID,Fuentealba Matias,Park JiwoonORCID,Narayanan S. Anand,Wu FeiORCID,Najjar DeenaORCID,Chin Christopher R.ORCID,Meydan CemORCID,Loy Conor,Mathyk BegumORCID,Klotz RemiORCID,Ortiz Veronica,Nguyen Khiem,Ryon Krista A.,Damle Namita,Houerbi Nadia,Patras Laura I.,Schanzer Nathan,Hutchinson Gwyneth A.ORCID,Foox Jonathan,Bhattacharya Chandrima,Mackay Matthew,Afshin Evan E.,Hirschberg Jeremy Wain,Kleinman Ashley S.,Schmidt Julian C.,Schmidt Caleb M.,Schmidt Michael A.,Beheshti AfshinORCID,Matei IrinaORCID,Lyden DavidORCID,Mullane Sean,Asadi Amran,Lenz Joan S.,Mzava Omary,Yu Min,Ganesan Saravanan,De Vlaminck IwijnORCID,Melnick Ari M.ORCID,Barisic DarkoORCID,Winer Daniel A.ORCID,Zwart Sara R.ORCID,Crucian Brian E.,Smith Scott M.ORCID,Mateus Jaime,Furman DavidORCID,Mason Christopher E.ORCID

Abstract

AbstractSpaceflight 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.

Publisher

Springer Science and Business Media LLC

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