Low-earth orbit spaceflight induces changes in circulating plasma small extracellular vesicle microRNA expression

A study led by researchers at Icahn School of Medicine at Mount Sinai suggests relatively short (median 12 days long) low‐Earth orbit (LEO) spaceflight induces changes in circulating plasma small extracellular vesicle (sEV) microRNA expression. Normalization of small RNA sequencing (sRNAseq) data and quantitative polymerase chain reaction (qPCR) validation confirmed miR‐4732‐3p is significantly upregulated up to 3 days post‐landing, and enrichment analysis suggests this miRNA is expressed in various central nervous system tissues and hematopoietic cells and may be linked to different organ disorders.

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(A) Schematic representation of experimental design and bioinformatics pipeline. The table shows non‐attributable demographic information, binned ages, of 14 astronauts who flew space Shuttle missions between 1998–2001. Peripheral blood was isolated from astronauts at three different time points: 10 days before launch (L‐10), day of return from mission (R‐0), and 3 days after return (R+3). sEVs were isolated from plasma, and sEV‐derived total RNA was processed for small RNA sequencing (sRNAseq). Differentially expressed microRNA (miRNAs) were identified using three computational pipelines: RUVseq+EdgeR, EdgeR+Limma, and EdgeR only. For the identified miRNA, pathway enrichment analysis was performed using Gene Ontology (GO) Term, 2021 Kyoto Encyclopedia of Genes and Genomes (KEGG), Online Mendelian Inheritance in Man (OMIM), and Jensen Tissue databases. (B, C) Characterization of exosomes by concentration and size using Nanosignt analysis. (D) Exosome isolation was further validated using an exosome‐specific antibody array (exosome markers: CD63, CD81, ALIX, FLOT1, ICAM1, EpCam, ANXA5, and TSG101). Cis‐Golgi marker GM130 monitors any cellular contamination in exosome isolation, and a positive control spot was derived from human serum exosomes. (E) Self‐organizing maps (SOM) transcriptomic portrayal projects high dimensional transcript expression data onto a 2D grid map. Each map expresses a transcriptome profile for each astronaut at L‐10, R‐0, and R+3 and is characterized by red‐blue spots that reflect up‐and downregulated miRNAs

Goukassian D, Arakelyan A, Brojakowska A, Bisserier M, Hakobyan S, Hadri L, Rai AK, Evans A, Sebastian A, Truongcao M, Gonzalez C, Bajpai A, Cheng Z, Dubey PK, Addya S, Mills P, Walsh K, Kishore R, Coleman M, Garikipati VNS. (2022) Space flight associated changes in astronauts’ plasma-derived small extracellular vesicle microRNA: Biomarker identification. Clin Transl Med 12(6):e845. [article]

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