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

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 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 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

doi:10.1038/s41467-024-49211-2

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

Nat Commun. 2024 Jun 11;15(1):4954. doi: 10.1038/s41467-024-49211-2.

Authors

JangKeun Kim^#^{1

2}, Braden T Tierney^#^{1

2}, Eliah G Overbey^{1

2

3

4}, Ezequiel Dantas^{5

6}, Matias Fuentealba⁷, Jiwoon Park^{1

2}, S Anand Narayanan⁸, Fei Wu⁷, Deena Najjar¹, Christopher R Chin^{2

9}, Cem Meydan^{1

2

10}, Conor Loy¹¹, Begum Mathyk¹², Remi Klotz¹³, Veronica Ortiz¹³, Khiem Nguyen⁷, Krista A Ryon¹, Namita Damle¹, Nadia Houerbi^{1

2}, Laura I Patras^{14

15}, Nathan Schanzer¹⁶, Gwyneth A Hutchinson^{17

18

19}, Jonathan Foox^{1

2}, Chandrima Bhattacharya^{2

9}, Matthew Mackay⁹, Evan E Afshin^{1

2}, Jeremy Wain Hirschberg^{1

2}, Ashley S Kleinman^{1

2}, Julian C Schmidt^{20

21}, Caleb M Schmidt^{20

21

22}, Michael A Schmidt^{20

21}, Afshin Beheshti^{23

24}, Irina Matei^{6

14}, David Lyden^{6

14}, Sean Mullane²⁵, Amran Asadi²⁵, Joan S Lenz¹¹, Omary Mzava¹¹, Min Yu¹³, Saravanan Ganesan^{6

10}, Iwijn De Vlaminck¹¹, Ari M Melnick^{6

10}, Darko Barisic^{6

10}, Daniel A Winer^{7

26

27

28

29}, Sara R Zwart³⁰, Brian E Crucian³¹, Scott M Smith³¹, Jaime Mateus²⁴, David Furman^{32

33

34}, Christopher E Mason^{35

36

37

38

39}

Affiliations

¹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 100221, USA.
² The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA.
³ Center for STEM, University of Austin, Austin, TX, USA.
⁴ BioAstra, Inc, New York, NY, USA.
⁵ Division of Endocrinology, Department of Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.
⁶ Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10065, USA.
⁷ Buck Artificial Intelligence Platform, Buck Institute for Research on Aging, Novato, CA, 94945, USA.
⁸ Department of Health, Nutrition, and Food Sciences, Florida State University, Tallahassee, FL, USA.
⁹ Tri-Institutional Biology and Medicine Program, Weill Cornell Medicine, New York, NY, 10021, USA.
¹⁰ Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
¹¹ Cornell University, Meinig School of Biomedical Engineering, Ithaca, NY, 14850, USA.
¹² Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
¹³ Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁴ Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
¹⁵ Department of Molecular Biology and Biotechnology, Center of Systems Biology, Biodiversity and Bioresources, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania.
¹⁶ School of Medicine, New York Medical College, Valhalla, NY, 10595, USA.
¹⁷ NASA Center for the Utilization of Biological Engineering in Space (CUBES), Berkeley, CA, 94720, USA.
¹⁸ Department of Bioengineering, University of California, Berkeley, Berkeley, CA, 94720, USA.
¹⁹ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
²⁰ Sovaris Aerospace, Boulder, CO, USA.
²¹ Advanced Pattern Analysis & Human Performance Group, Boulder, CO, USA.
²² Department of Systems Engineering, Colorado State University, Fort Collins, CO, USA.
²³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
²⁴ Blue Marble Space Institute of Science, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, 94035, USA.
²⁵ Space Exploration Technologies Corporation (SpaceX), Hawthorne, CA, USA.
²⁶ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089, USA.
²⁷ Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
²⁸ Division of Cellular & Molecular Biology, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, M5G 1L7, Canada.
²⁹ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
³⁰ University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA.
³¹ Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Human Health and Performance Directorate, 2101 NASA Parkway, Houston, TX, 77058, USA.
³² Buck Artificial Intelligence Platform, Buck Institute for Research on Aging, Novato, CA, 94945, USA. [email protected].
³³ Stanford 1000 Immunomes Project, Stanford School of Medicine, Stanford, CA, 94306, USA. [email protected].
³⁴ Instituto de Investigaciones en Medicina Traslacional (IIMT), Universidad Austral, CONICET, Pilar, Argentina. [email protected].
³⁵ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 100221, USA. [email protected].
³⁶ The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA. [email protected].
³⁷ Tri-Institutional Biology and Medicine Program, Weill Cornell Medicine, New York, NY, 10021, USA. [email protected].
³⁸ The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10021, USA. [email protected].
³⁹ WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, 10021, USA. [email protected].

^# Contributed equally.

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.

MeSH terms

Animals
Astronauts
Cytokines / metabolism
Female
Gene Expression Profiling
Humans
Male
Mice
Oxidative Phosphorylation
Sex Factors
Single-Cell Analysis*
Space Flight*
T-Lymphocytes / immunology
Transcriptome*

Substances

Cytokines

Abstract

MeSH terms

Substances

Grants and funding