Cell-free DNA (cfDNA) and Exosome Profiling from a Year-Long Human Spaceflight Reveals Circulating Biomarkers

Daniela Bezdan; Kirill Grigorev; Cem Meydan; Fanny A Pelissier Vatter; Michele Cioffi; Varsha Rao; Matthew MacKay; Kiichi Nakahira; Philip Burnham; Ebrahim Afshinnekoo; Craig Westover; Daniel Butler; Chris Mozsary; Timothy Donahoe; Jonathan Foox; Tejaswini Mishra; Serena Lucotti; Brinda K Rana; Ari M Melnick; Haiying Zhang; Irina Matei; David Kelsen; Kenneth Yu; David C Lyden; Lynn Taylor; Susan M Bailey; Michael P Snyder; Francine E Garrett-Bakelman; Stephan Ossowski; Iwijn De Vlaminck; Christopher E Mason

doi:10.1016/j.isci.2020.101844

Cell-free DNA (cfDNA) and Exosome Profiling from a Year-Long Human Spaceflight Reveals Circulating Biomarkers

iScience. 2020 Nov 25;23(12):101844. doi: 10.1016/j.isci.2020.101844. eCollection 2020 Dec 18.

Authors

Daniela Bezdan^{1

2}, Kirill Grigorev¹, Cem Meydan^{1

3

4}, Fanny A Pelissier Vatter⁵, Michele Cioffi⁵, Varsha Rao⁶, Matthew MacKay¹, Kiichi Nakahira⁷, Philip Burnham⁸, Ebrahim Afshinnekoo^{1

3

4}, Craig Westover¹, Daniel Butler¹, Chris Mozsary¹, Timothy Donahoe¹, Jonathan Foox¹, Tejaswini Mishra⁶, Serena Lucotti⁵, Brinda K Rana⁹, Ari M Melnick¹⁰, Haiying Zhang¹¹, Irina Matei⁵, David Kelsen¹¹, Kenneth Yu¹¹, David C Lyden⁵, Lynn Taylor¹², Susan M Bailey¹², Michael P Snyder⁶, Francine E Garrett-Bakelman^{10

13

14

15}, Stephan Ossowski¹⁶, Iwijn De Vlaminck¹⁷, Christopher E Mason^{1

3

4

18}

Affiliations

¹ Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA.
² Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital, Tubingen, Germany.
³ The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
⁴ The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA.
⁵ 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 Medical College, New York, NY, USA.
⁶ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Nara Medical University, Kashihara, Nara, Japan.
⁸ Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹ Department of Psychiatry University of California, San Diego, La Jolla, CA, USA.
¹⁰ Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
¹¹ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹² Department of Environmental & Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
¹³ Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
¹⁴ Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA.
¹⁵ University of Virginia Cancer Center, Charlottesville, VA, USA.
¹⁶ Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
¹⁷ Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
¹⁸ The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.

Abstract

Liquid biopsies based on cell-free DNA (cfDNA) or exosomes provide a noninvasive approach to monitor human health and disease but have not been utilized for astronauts. Here, we profile cfDNA characteristics, including fragment size, cellular deconvolution, and nucleosome positioning, in an astronaut during a year-long mission on the International Space Station, compared to his identical twin on Earth and healthy donors. We observed a significant increase in the proportion of cell-free mitochondrial DNA (cf-mtDNA) inflight, and analysis of post-flight exosomes in plasma revealed a 30-fold increase in circulating exosomes and patient-specific protein cargo (including brain-derived peptides) after the year-long mission. This longitudinal analysis of astronaut cfDNA during spaceflight and the exosome profiles highlights their utility for astronaut health monitoring, as well as cf-mtDNA levels as a potential biomarker for physiological stress or immune system responses related to microgravity, radiation exposure, and the other unique environmental conditions of spaceflight.

Keywords: Omics; Space Medicine.

Abstract

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