Multi-Omic, Single-Cell, and Biochemical Profiles of Astronauts Guide Pharmacological Strategies for Returning to Gravity

Gertz, Monica; Chin, Christopher R.; Tomoiaga, Delia; Chang, Christina; Butler, Daniel; Afshinnekoo, Ebrahim; Mozsary, Chris; Donahoe, Timothy; Bezdan, Daniela; Schmidt, Michael A.; Melnick, Ari; Garrett-Bakelman, Francine E.; Crucian, Brian; Lee, Stuart M. C.; Zwart, Sara R.; Smith, Scott M.; Meydan, Cem; Mason, Christopher E.

doi:10.2139/ssrn.3682827

Cited by 10 publications

(13 citation statements)

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“…Our analyses suggest that systemic shifts in mitochondrial function occur in spaceflight in most of the tissues we examined. Mitochondrial changes likely impact processes such as innate immunity, lipid metabolism, and gene regulation in both mice and humans, and the results from our analyses are consistent with those from previous studies (Beheshti et al, 2019;Suomalainen and Battersby, 2018) and are supported by multiple other omics studies (Bezdan et al, 2020;Gertz et al, 2020). Raising awareness for adverse health outcomes during spaceflight will help guide scientific community responses to mitigate spaceflight-associated health risks and develop appropriate countermeasures.…”

Section: Discussionsupporting

confidence: 88%

“…Here, we provide an integrated analysis of mammalian space biology using a systems biology approach powered by multiple ''omic'' platforms. Realized by the existence of NASA's GeneLab (https://genelab.nasa.gov/) (Ray et al, 2019), a dedicated space omics database, our work includes 4 human cell models, 13 different tissues (11 mouse and 2 human), 2 mouse strains (C57BL/6 and BALB/C), and space missions ranging from 2006 to 2017, culminating in the measurement of astronaut blood and urine metabolites, as well as transcriptional data from the NASA Twin Study (Garrett-Bakelman et al, 2019;Gertz et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

Silveira

Fazelinia

Rosenthal

et al. 2020

Cell

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244

191

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

Silveira

Fazelinia

Rosenthal

et al. 2020

Cell

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244

191

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“…revealed that TW exosomes were enriched in proteins involved in proteasome pathways (Figure 6H). TW exosomes also packaged CD14, a pro-inflammatory monocyte marker, consistent with the increase in CD14 + monocytes observed post-return to gravity in immune markers studied upon return to Earth (Gertz et al, 2020). Notably, basigin and integrin b1 proteins, which are correlated with cancer progression and inflammation (Hoshino et al, , 2020Keller et al, 2009;Yoshioka et al, 2014), were also detected in TW exosomes but not in HR or healthy control exosomes.…”

Section: Analysis Of Plasma-circulating Exosomes Post-flightsupporting

confidence: 64%

“…These longduration missions and the increasing exposure of humans to spaceflight-specific conditions necessitate the study of molecular changes in the human body induced by exposure to spaceflight stressors such as microgravity, radiation, noise, restricted diet, and reduced physical work opportunities. The NASA Twins Study (Garrett-Bakelman et al, 2019) enabled interrogation of the impact of prolonged spaceflight on the human biology and cell-to-cell variations in the immune system (Gertz et al, 2020); however, there has never been a study on the impact of spaceflight on cell-free DNA (cfDNA).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…The compact size of the smartphone microscope is useful not only for its portability but also for applications in space. Stress and damage to cells in weightless space are important for study in space exploration [ 25 , 26 , 27 ]. Because of the limited space available in a spacecraft and space stations, it is essential that the measurement equipment used are as compact as possible with minimal components.…”

Section: Discussionmentioning

confidence: 99%

Smartphone-Based Portable Bioluminescence Imaging System Enabling Observation at Various Scales from Whole Mouse Body to Organelle

Hattori

Shirane²,

Matsuda

et al. 2020

Sensors

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Current smartphones equipped with high-sensitivity and high-resolution sensors in the camera can respond to the needs of low-light imaging, streaming acquisition, targets of various scales, etc. Therefore, a smartphone has great potential as an imaging device even in the scientific field and has already been introduced into biomolecular imaging using fluorescence tags. However, owing to the necessity of an excitation light source, fluorescence methods impair its mobility. Bioluminescence does not require illumination; therefore, imaging with a smartphone camera is compact and requires minimal devices, thus making it suitable for personal and portable imaging devices. Here, we report smartphone-based methods to observe biological targets in various scales using bioluminescence. In particular, we demonstrate, for the first time, that bioluminescence can be observed in an organelle in a single living cell using a smartphone camera by attaching a detachable objective lens. Through capturing color changes with the camera, changes in the amount of target molecules was detected using bioluminescent indicators. The combination of bioluminescence and a mobile phone makes possible a compact imaging system without an external light source and expands the potential of portable devices.

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Multi-Omic, Single-Cell, and Biochemical Profiles of Astronauts Guide Pharmacological Strategies for Returning to Gravity

Cited by 10 publications

References 0 publications

Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

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

Smartphone-Based Portable Bioluminescence Imaging System Enabling Observation at Various Scales from Whole Mouse Body to Organelle

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