Dataset Information

Clonal Hematopoiesis Before, During, and After Human Spaceflight.

ABSTRACT: Clonal hematopoiesis (CH) occurs when blood cells harboring an advantageous mutation propagate faster than others. These mutations confer a risk for hematological cancers and cardiovascular disease. Here, we analyze CH in blood samples from a pair of twin astronauts over 4 years in bulk and fractionated cell populations using a targeted CH panel, linked-read whole-genome sequencing, and deep RNA sequencing. We show CH with distinct mutational profiles and increasing allelic fraction that includes a high-risk, TET2 clone in one subject and two DNMT3A mutations on distinct alleles in the other twin. These astronauts exhibit CH almost two decades prior to the mean age at which it is typically detected and show larger shifts in clone size than age-matched controls or radiotherapy patients, based on a longitudinal cohort of 157 cancer patients. As such, longitudinal monitoring of CH may serve as an important metric for overall cancer and cardiovascular risk in astronauts.

SUBMITTER: Mencia-Trinchant N

PROVIDER: S-EPMC9398182 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Clonal Hematopoiesis Before, During, and After Human Spaceflight.

Mencia-Trinchant Nuria N MacKay Matthew J MJ Chin Christopher C Afshinnekoo Ebrahim E Foox Jonathan J Meydan Cem C Butler Daniel D Mozsary Christopher C Vernice Nicholas A NA Darby Charlotte C Schatz Michael C MC Bailey Susan M SM Melnick Ari M AM Guzman Monica L ML Bolton Kelly K Braunstein Lior Z LZ Garrett-Bakelman Francine F Levine Ross L RL Hassane Duane C DC Mason Christopher E CE

Cell reports 20201125 10

Clonal hematopoiesis (CH) occurs when blood cells harboring an advantageous mutation propagate faster than others. These mutations confer a risk for hematological cancers and cardiovascular disease. Here, we analyze CH in blood samples from a pair of twin astronauts over 4 years in bulk and fractionated cell populations using a targeted CH panel, linked-read whole-genome sequencing, and deep RNA sequencing. We show CH with distinct mutational profiles and increasing allelic fraction that include ...[more]

PMID: 33242405

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Project description:Introduction: During exploratory space flights astronauts risk exposure to toxic planetary dust. Exhaled nitric oxide partial pressure (PENO) is a simple method to monitor lung health by detecting airway inflammation after dust inhalation. The turnover of NO in the lungs is dependent on several factors which will be altered during planetary exploration such as gravity (G) and gas density. To investigate the impacts of these factors on normal PENO, we took measurements before and during a stay at the International Space Station, at both normal and reduced atmospheric pressures. We expected stable PENO levels during the preflight and inflight periods, with lower values inflight. With reduced pressure we expected no net changes of PENO. Material and methods: Ten astronauts were studied during the pre-flight (1 G) and inflight (µG) periods at normal pressure [1.0 ata (atmospheres absolute)], with six of them also monitored at reduced (0.7 ata) pressure and gas density. The average observation period was from 191 days before launch until 105 days after launch. PENO was measured together with estimates of alveolar NO and the airway contribution to the exhaled NO flux. Results: The levels of PENO at 50 mL/s (PENO50) were not stable during the preflight and inflight periods respectively but decreased with time (p = 0.0284) at a rate of 0.55 (0.24) [mean (SD)] mPa per 180 days throughout the observation period, so that there was a significant difference (p < 0.01, N = 10) between gravity conditions. Thus, PENO50 averaged 2.28 (0.70) mPa at 1 G and 1.65 (0.51) mPa during µG (-27%). Reduced atmospheric pressure had no net impact on PENO50 but increased the airway contribution to exhaled NO. Discussion: The time courses of PENO50 suggest an initial airway inflammation, which gradually subsided. Our previous hypothesis of an increased uptake of NO to the blood by means of an expanded gas-blood interface in µG leading to decreased PENO50 is neither supported nor contradicted by the present findings. Baseline PENO50 values for lung health monitoring in astronauts should be obtained not only on ground but also during the relevant gravity conditions and before the possibility of inhaling toxic planetary dust.

Dataset Information

Clonal Hematopoiesis Before, During, and After Human Spaceflight.

Publications

Clonal Hematopoiesis Before, During, and After Human Spaceflight.

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