Astronauts Plasma-Derived Exosomes Induced Aberrant EZH2-Mediated H3K27me3 Epigenetic Regulation of the Vitamin D Receptor.
Astronauts Plasma-Derived Exosomes Induced Aberrant EZH2-Mediated H3K27me3 Epigenetic Regulation of the Vitamin D Receptor.
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DOI：
10.3389/fcvm.2022.855181
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发表时间：
2022
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
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作者：
在航天环境中有独特的压力源。暴露于这些压力源可能会对宇航员的健康产生不利影响，包括增加患癌症和心血管疾病的风险。小细胞外囊泡（sev，即外泌体）在细胞间通讯和调节各种生物过程中起着至关重要的作用，有助于它们在疾病发病机制中发挥作用。为了评估太空飞行是否会改变sev转录组谱，从3名宇航员在两个不同时间点的血浆中分离出sev：发射前10天（L-10）和从航天飞机任务返回后3天（R+3）。用L-10和R+3宇航员来源的外泌体处理AC16细胞24小时。分离总RNA，并使用Affymetrix微阵列分析基因表达谱。富集分析使用Enrichment进行。利用ENCODE/ChEA Consensus TF数据库进行转录因子（TF）富集分析，发现与L-10宇航员来源外显体处理的细胞相比，R+3处理的AC16细胞中与多梳抑制复合体2 （PRC2）和维生素D受体（VDR）相关的基因集。使用来自Roadmap表观基因组学计划的数据集进一步分析组蛋白修饰，证实了与H3K27me3抑制标记相关的基因集的富集。有趣的是，对先前发表的H3K27me3 -染色质免疫沉淀测序（ChIP-Seq） ENCODE数据集的分析显示，H3K27me3在VDR启动子中富集。总之，我们的研究结果表明，航天员衍生的sev可能通过促进PRC2复合物和H3K27me3水平的激活，从表观遗传学上抑制成人心肌细胞中VDR的表达。
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.
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影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
影响因子：
5.6
作者：
Bisserier M;Katz MG;Bueno-Beti C;Brojakowska A;Zhang S;Gubara S;Kohlbrenner E;Fazal S;Fargnoli A;Dorfmuller P;Humbert M;Hata A;Goukassian DA;Sassi Y;Hadri L
通讯作者：
Hadri L
影响因子：
4.2
作者：
Kheiri B;Abdalla A;Osman M;Ahmed S;Hassan M;Bachuwa G
通讯作者：
Bachuwa G
影响因子：
5.4
作者：
Bisserier M;Shanmughapriya S;Rai AK;Gonzalez C;Brojakowska A;Garikipati VNS;Madesh M;Mills PJ;Walsh K;Arakelyan A;Kishore R;Hadri L;Goukassian DA
通讯作者：
Goukassian DA