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

TitleSingle-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight.
Publication TypeJournal Article
Year of Publication2024
AuthorsKim JK, Tierney BT, Overbey EG, Dantas E, Fuentealba M, Park J, S Narayanan A, Wu F, Najjar D, Chin CR, Meydan C, Loy C, Mathyk B, Klotz R, Ortiz V, Nguyen K, Ryon KA, Damle N, Houerbi N, Patras LI, Schanzer N, Hutchinson GA, Foox J, Bhattacharya C, MacKay M, Afshin EE, Hirschberg JWain, Kleinman AS, Schmidt JC, Schmidt CM, Schmidt MA, Beheshti A, Matei I, Lyden D, Mullane S, Asadi A, Lenz JS, Mzava O, Yu M, Ganesan S, De Vlaminck I, Melnick AM, Barisic D, Winer DA, Zwart SR, Crucian BE, Smith SM, Mateus J, Furman D, Mason CE
JournalNat Commun
Volume15
Issue1
Pagination4954
Date Published2024 Jun 11
ISSN2041-1723
KeywordsAnimals, Astronauts, Cytokines, Female, Gene Expression Profiling, Humans, Male, Mice, Oxidative Phosphorylation, Sex Factors, Single-Cell Analysis, Space Flight, T-Lymphocytes, Transcriptome
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.

DOI10.1038/s41467-024-49211-2
Custom 1

https://www.ncbi.nlm.nih.gov/pubmed/38862516?dopt=Abstract

Alternate JournalNat Commun
PubMed ID38862516
PubMed Central IDPMC11166952
Grant ListR01 CA249054 / CA / NCI NIH HHS / United States
80NSSC22K0254 / / NASA | Johnson Space Center (JSC) /
R01 AI151059 / AI / NIAID NIH HHS / United States
NNH18ZTT001N-FG2 / / NASA | Johnson Space Center (JSC) /
P01 CA214274 / CA / NCI NIH HHS / United States
NNX17AB26G / / NASA | Johnson Space Center (JSC) /
R35 CA220499 / CA / NCI NIH HHS / United States
R01 MH117406 / MH / NIMH NIH HHS / United States

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