Dataset Information

Proteomic analysis of two populations of Schistosoma mansoni-derived extracellular vesicles: exosome-like vesicles and microvesicles

ABSTRACT: Extracellular vesicles (EVs) have been characterized from many species of parasitic helminths, and recent experimental evidence supports important functions for their cargo in host-parasite relationships. Here, we carried out a detailed proteomic analysis of two populations of EVs – exosome like vesicles (ELVs) and microvesicles (MVs) – from Schistosoma mansoni. We profiled the proteins present in these EVs (including external trypsin-liberated peptides, cargo proteins, integral membrane proteins (IMPs) and peripheral membrane proteins (PMPs) using LC-MS/MS.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Schistosoma Mansoni (blood Fluke)

SUBMITTER: Javier Sotillo

LAB HEAD: Javier Sotillo

PROVIDER: PXD015857 | Pride | 2019-10-17

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	S_mansoniMV_IMP_mzml.mzid.gz	Mzid
	S_mansoniMVs_PMPs_mzml.mzid.gz	Mzid
	S_mansoniMVs_cargo_mzml.mzid.gz	Mzid
	S_mansoni_MV_shaving_mzml.mzid.gz	Mzid
	S_mansoniexosomes_Cargo_mzml.mzid.gz	Mzid

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Publications

Proteomic analysis of two populations of Schistosoma mansoni-derived extracellular vesicles: 15k pellet and 120k pellet vesicles.

Kifle Desalegn Woldeyohannes DW Pearson Mark S MS Becker Luke L Pickering Darren D Loukas Alex A Sotillo Javier J

Molecular and biochemical parasitology 20200131

Helminth parasites secrete extracellular vesicles (EVs) into their environment that have potential roles in host-parasite communication, and thus represent potentially useful targets for novel control strategies. Here, we carried out a comprehensive proteomic analysis of two different populations of EVs - 15k pellet and 120k pellet EVs - from Schistosoma mansoni adult worms. We characterised the proteins present in the membranes of the EVs (including external trypsin-liberated peptides, integral ...[more]

PMID: 32014446

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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.