Cell-free DNA (cfDNA) and exosome profiling from a year-long human spaceflight reveals circulating biomarkers
Cell-free DNA (cfDNA) and exosome profiling from a year-long human spaceflight reveals circulating biomarkers
Abstract The health impact of prolonged space flight on the human body is not well understood. Liquid biopsies based on cell-free DNA (cfDNA) or exosome analysis provide a noninvasive approach to monitor the dynamics of genomic, epigenomic and proteomic biomarkers, and the occurrence of DNA damage, physiological stress, and immune responses. To study the molecular consequences of spaceflight we profiled cfDNA isolated from plasma of an astronaut (TW) during a year-long mission on the International Space Station (ISS), sampling before, during, and after spaceflight, and compared the results to cfDNA profiling of the subject’s identical twin (HR) who remained on Earth, as well as healthy donors. We characterized cfDNA concentration and fragment size, and the positioning of nucleosomes on cfDNA, observing a significant increase in the proportion of cell-free mitochondrial DNA inflight, suggesting that cf-mtDNA is a potential biomarker for space flight-associated stress, and that this result was robust to ambient transit from the International Space Station (ISS). Analysis of exosomes isolated from post-flight plasma revealed a 30-fold increase in circulating exosomes and distinct exosomal protein cargo, including brain-derived peptides, in TW compared to HR and all known controls. This study provides the first longitudinal analysis of astronaut cfDNA during spaceflight, as well as the first exosome profiles, and highlights cf-mtDNA levels as a potential biomarker for physiological stress or immune system responses related to microgravity, radiation exposure, and other unique environmental conditions on the ISS.
Bailey Susan M、P.Snyder Michael、Mason Christopher E.、Meydan Cem、Pelissier Vatter Fanny A.、Burnham Philip、MacKay Matthew、Lucotti Serena、Ossowski Stephan、Moszary Chris、Grigorev Kirill、Butler Daniel、Lyden David C、Bezdan Daniela、Westover Craig、Cioffi Michele、Zhang Haiying、Yu Kenneth、Nakahira Kiichi、Melnick Ari M.、Foox Jonathan、Garrett-Bakelman Francine E.、Rana Brinda K.、Mishra Tejaswini、Taylor Lynn、Rao Varsha、Kelsen David、De Vlaminck Iwijn、Afshinnekoo Ebrahim、Matei Irina
Department of Environmental & Radiological Health Sciences, Colorado State UniversityDepartment of Genetics, Stanford University School of MedicineDepartment of Physiology and Biophysics, Weill Cornell Medicine||The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine||The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine||The Feil Family Brain and Mind Research Institute, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineChildren?ˉs Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children?ˉs Health, Meyer Cancer Center, Weill Cornell Medical CollegeDepartment of Bioengineering, University of PennsylvaniaDepartment of Physiology and Biophysics, Weill Cornell MedicineChildren?ˉs Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children?ˉs Health, Meyer Cancer Center, Weill Cornell Medical CollegeInstitute of Medical Genetics and Applied Genomics, University of T¨1bingenDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineChildren?ˉs Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children?ˉs Health, Meyer Cancer Center, Weill Cornell Medical CollegeDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineChildren?ˉs Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children?ˉs Health, Meyer Cancer Center, Weill Cornell Medical CollegeDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterNara Medical UniversityDepartment of Medicine, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Medicine, University of Virginia School of Medicine||Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine||University of Virginia Cancer CenterDepartment of Psychiatry University of CaliforniaDepartment of Genetics, Stanford University School of MedicineDepartment of Environmental & Radiological Health Sciences, Colorado State UniversityDepartment of Genetics, Stanford University School of MedicineDepartment of Medicine, Memorial Sloan Kettering Cancer CenterNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell UniversityDepartment of Physiology and Biophysics, Weill Cornell Medicine||The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine||The WorldQuant Initiative for Quantitative Prediction, Weill Cornell MedicineChildren?ˉs Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children?ˉs Health, Meyer Cancer Center, Weill Cornell Medical College
航天生物科学研究方法、生物科学研究技术基础医学
NASAcfDNAliquid biopsymtDNAmtRNAexosomesInternational Space StationNASA Twins Study
Bailey Susan M,P.Snyder Michael,Mason Christopher E.,Meydan Cem,Pelissier Vatter Fanny A.,Burnham Philip,MacKay Matthew,Lucotti Serena,Ossowski Stephan,Moszary Chris,Grigorev Kirill,Butler Daniel,Lyden David C,Bezdan Daniela,Westover Craig,Cioffi Michele,Zhang Haiying,Yu Kenneth,Nakahira Kiichi,Melnick Ari M.,Foox Jonathan,Garrett-Bakelman Francine E.,Rana Brinda K.,Mishra Tejaswini,Taylor Lynn,Rao Varsha,Kelsen David,De Vlaminck Iwijn,Afshinnekoo Ebrahim,Matei Irina.Cell-free DNA (cfDNA) and exosome profiling from a year-long human spaceflight reveals circulating biomarkers[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/2020.11.08.373530.点此复制
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