Document Type
Article
Publication Date
6-16-2022
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.
Recommended Citation
Bisserier, Malik; Brojakowska, Agnieszka; Saffran, Nathaniel; Rai, Amit Kumar; Lee, Brooke; Coleman, Matthew; Sebastian, Aimy; Evans, Angela; Mills, Paul J; Addya, Sankar; Arakelyan, Arsen; Garikipati, Venkata Naga Srikanth; Hadri, Lahouaria; and Goukassian, David A, "Astronauts Plasma-Derived Exosomes Induced Aberrant EZH2-Mediated H3K27me3 Epigenetic Regulation of the Vitamin D Receptor" (2022). Kimmel Cancer Center Faculty Papers. Paper 93.
https://jdc.jefferson.edu/kimmelccfp/93
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
35783863
Language
English
Comments
This article is the author's final published version in Frontiers in Cardiovascular Medicine, Volume 9, June 2022, Article number 855181. This article was first published by Frontiers Media, S.A.
The published version is available at https://doi.org/10.3389/fcvm.2022.855181.
Copyright © 2022 Bisserier, Brojakowska, Saffran, Rai, Lee, Coleman, Sebastian, Evans, Mills, Addya, Arakelyan, Garikipati, Hadri and Goukassian.
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