Extracellular Vesicles in acute coronary syndrome: carrier of epigenetics marks
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ABSTRACT:
PROVIDER: PRJEB52398 | ENA |
REPOSITORIES: ENA
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Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.
2023-04-03 | E-MTAB-11641 | biostudies-arrayexpress
Project description:Small extracellular vesicles (sEVs)-derived circular RNAs (circRNAs) could regulate gene expression in recipient cells, and dysregulation of sEVs-derived circRNAs has been implicated in several diseases. However, the expression and function of sEVs-derived circRNAs in coronary atherosclerosis (CAD) remain unknown. In this study, we investigated global changes in the expression patterns of circRNAs in sEVs from coronary atherosclerosis-related monocytes.
2021-10-20 | GSE166126 | GEO
Project description:We have investigated the genomic and epigenetic consequences of co-culturing colorectal carcinoma cells with membrane vesicles from pathogenic bacteria Vibrio cholerae and non-pathogenic commensal bacteria Escherichia coli. Our study has revealed that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of coloncarcinoma cells. The changes in gene expression correlated positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. Moreover, we have demonstrated that membrane vesicles obtained only from V. cholerae induced the expression of genes associated with tumour differentiation. Altogether, our study suggests that the observed genomic changes in host cells might be due to specific components of membrane vesicles and does not require communication by direct contact with the bacteria.
2017-08-23 | GSE102923 | GEO
Project description:Expression profiles of RNA from monocyte-derived small extracellular vesicles in coronary atherosclerosis
| PRJNA699305 | ENA
Project description:Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation.
2012-11-05 | GSE25252 | GEO
Project description:Epigenetics and Alternative Splicing are both critical mechanisms guiding gene expression. Several studies have demonstrated that epigenetic marks can influence alternative splicing decisions, but less is known about how alternative splicing may impact epigenetics. Here, we demonstrate that several genes encoding histone modifying enzymes are alternatively spliced downstream of T cell activation signaling pathways, including HDAC7, a gene previously implicated in controlling gene expression programs and differentiation in T cells. Using CRISPR-Cas9 gene editing and cDNA expression, we show that differential inclusion of HDAC7 exon 9 controls the interaction of HDAC7 with protein chaperones with resulting impact on histone modifications and gene expression. Notably, the long isoform, which is favored upon JNK signaling, promotes expression of several critical T cell surface proteins including CD3, CD28, CD69. Thus, we demonstrate that alternative splicing of HDAC7 has a global impact on epigenetics and gene expression, and may contribute to T cell regulation.
2023-02-18 | PXD036471 | Pride
Project description:Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation. GFP+CD4+ and GFP-CD4+ splenocytes were sorted from DEREG and DEREG/Scurfy mice. These cells were activated with anti-CD3/CD28 antibodies, and then transduced with Foxp3-expressing retrovirus (pGCSamIN, NGFR marker). NGFR+ T cells sorted were subjected to microarray analysis (Affymetrix, mouse genome 430 2.0 array). To normalize the experimental conditions, Tregs (GFP+ T cells from DEREG) and Tconv (GFP- T cells from DEREG) were also activated and transduced with empty vector. Two replicates each.
2012-11-05 | E-GEOD-25252 | biostudies-arrayexpress