iScience (Dec 2020)
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
Affiliations
- Daniela Bezdan
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA; Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital, Tubingen, Germany
- Kirill Grigorev
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA
- Cem Meydan
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA
- Fanny A. Pelissier Vatter
- 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
- Michele Cioffi
- 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
- Varsha Rao
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
- Matthew MacKay
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA
- Kiichi Nakahira
- Nara Medical University, Kashihara, Nara, Japan
- Philip Burnham
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
- Ebrahim Afshinnekoo
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA
- Craig Westover
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA
- Daniel Butler
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA
- Chris Mozsary
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA
- Timothy Donahoe
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA
- Jonathan Foox
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA
- Tejaswini Mishra
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
- Serena Lucotti
- 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
- Brinda K. Rana
- Department of Psychiatry University of California, San Diego, La Jolla, CA, USA
- Ari M. Melnick
- Department of Medicine, Weill Cornell Medicine, New York, NY, USA
- Haiying Zhang
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Irina Matei
- 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
- David Kelsen
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Kenneth Yu
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- David C. Lyden
- 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
- Lynn Taylor
- Department of Environmental & Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA
- Susan M. Bailey
- Department of Environmental & Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA
- Michael P. Snyder
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
- Francine E. Garrett-Bakelman
- Department of Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA; University of Virginia Cancer Center, Charlottesville, VA, USA
- Stephan Ossowski
- Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
- Iwijn De Vlaminck
- Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA
- Christopher E. Mason
- Department of Physiology and Biophysics, Weill Cornell Medicine, 1305 York Avenue, Y13-05, New York, NY 10021, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; Corresponding author
- Journal volume & issue
-
Vol. 23,
no. 12
p. 101844
Abstract
Summary: 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.
