Astronauts Plasma-Derived Exosomes Induced Aberrant EZH2-Mediated H3K27me3 Epigenetic Regulation of the Vitamin D Receptor
Year: 2022
Type: article
Abstract: There are unique stressors in the spaceflight environment. Exposure to such stressors may be associated with adverse effects on astronauts' health, including increased cancer and cardiovascular disease risks. Small extracellular vesicles (sEVs, i.e., exosomes) play a vital role in intercellular communication and regulate various biological processes contributing to their role in disease pathogenesis. To assess whether spaceflight alters sEVs transcriptome profile, sEVs were isolated from the blood plasma of 3 astronauts at two different time points: 10 days before launch (L-10) and 3 days after return (R+3) from the Shuttle mission. AC16 cells (human cardiomyocyte cell line) were treated with L-10 and R+3 astronauts-derived exosomes for 24 h. Total RNA was isolated and analyzed for gene expression profiling using Affymetrix microarrays. Enrichment analysis was performed using Enrichr. Transcription factor (TF) enrichment analysis using the ENCODE/ChEA Consensus TF database identified gene sets related to the polycomb repressive complex 2 (PRC2) and Vitamin D receptor (VDR) in AC16 cells treated with R+3 compared to cells treated with L-10 astronauts-derived exosomes. Further analysis of the histone modifications using datasets from the Roadmap Epigenomics Project confirmed enrichment in gene sets related to the H3K27me3 repressive mark. Interestingly, analysis of previously published H3K27me3-chromatin immunoprecipitation sequencing (ChIP-Seq) ENCODE datasets showed enrichment of H3K27me3 in the VDR promoter. Collectively, our results suggest that astronaut-derived sEVs may epigenetically repress the expression of the VDR in human adult cardiomyocytes by promoting the activation of the PRC2 complex and H3K27me3 levels.
Institutions: Icahn School of Medicine at Mount Sinai, The Ohio State University Wexner Medical Center, Lawrence Livermore National Laboratory, University of California, Davis, University of California San Diego, Thomas Jefferson University, Sidney Kimmel Cancer Center, Russian-Armenian University, Institute of Molecular Biology, National Academy of Sciences of Armenia
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
Funders: U.S. Department of Energy, National Aeronautics and Space Administration, American Heart Association, Ohio State University, National Academy of Sciences of Armenia, Cardiovascular Medical Research and Education Fund, Nuclear Safety and Security Commission, National Institutes of Health, National Heart, Lung, and Blood Institute, Lawrence Livermore National Laboratory
Awards: G1356433355, G14554683, G2102758578, Role of CircRNAs in Ischemic Tissue Repair and Regeneration, G3368592426, G3608168065, Investigating circular RNA as novel therapeutic targets for cardiac repair and regeneration, G5776719013, Training Program in Molecular and Cellular Cardiology, G6240043616, Extracellular vesicles secreted by human Induced Pluripotent Stem Cells (iPSC)-derived Vascular Cells as Novel Biomarker, G6670844962, G895790057, Interactions of SERCA2a and BMPRII in Vascular Disease, Role of Epac1 in the Pathogenesis of Pulmonary Fibrosis
OpenAlex ID: W4282964510