A novel community driven software for functional enrichment analysis of extracellular vesicles data

Pathan, Mohashin; Keerthikumar, Shivakumar; Chisanga, David; Alessandro, Riccardo; Ang, Ching‐Seng; Askenase, Philip W.; Batagov, Arsen O.; Benito-Martín, Alberto; Camussi, Giovanni; Clayton, Aled; Collino, Federica; Vizio, Dolores Di; Falcón‐Pérez, Juan Manuel; Fonseca, Pedro; Fonseka, Pamali; Fontana, Simona; Gho, Yong Song; Hendrix, An; Hoen, Esther N. M. Nolte‐‘t; Iraci, Nunzio; Kastaniegaard, Kenneth; Kislinger, Thomas; Kowal, Joanna; Kurochkin, Igor V.; Leonardi, Tommaso; Liang, Yaxuan; Llorente, Alicia; Lunavat, Taral R.; Maji, Sayantan; Monteleone, Francesca; Øverbye, Anders; Panaretakis, Theocharis; Patel, Tushar; Peinado, Héctor; Pluchino, ﻿Stefano; Principe, Stefania; Ronquist, K. Göran; Royo, Félix; Sahoo, Susmita; Spinelli, Cristiana; Stensballe, Allan; Théry, Clotilde; Herwijnen, Martijn J. C. van; Wauben, Marca H. M.; Welton, Joanne L.; Zhao, Kening; Mathivanan, Suresh

doi:10.1080/20013078.2017.1321455

Cited by 315 publications

(275 citation statements)

References 9 publications

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“…To predict the potential molecular function of miR-7116-5p, we use TargetScan, a popular bioinformatics tool to analyze 5795 predicted gene targets of miR-7116-5p, and then use Funrich software for molecular function enrichment analysis [34]. Figure 4B shows the percentage of genes predicted to be involved in molecular function of miR-7116-5p, including regulation of protein polyubiquitination, GTP binding, and ATP binding.…”

Section: Resultsmentioning

confidence: 99%

Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis

Shen

et al. 2018

J. of Cardiovasc. Trans. Res.

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We demonstrated the effects of exosomes secreted by cardiac mesenchymal stem cells (C-MSC-Exo) in protecting acute ischemic myocardium from reperfusion injury. To investigate the effect of exosomes from C-MSC on angiogenesis. We injected C-MSC-Exo or PBS intramuscularly into ischemic hind limb. Blood perfusion of limb was evaluated by laser Doppler Imaging. We observed that ischemic limb treated with C-MSC-Exo exhibit improved blood perfusion compared to ischemic limb treated with PBS at 2 weeks and 1 month after induction of limb ischemia. To explore the potential mechanisms underlying C-MSC-Exo’s angiogenetic effect, we performed microRNA array analysis, and identify mmu-miR-7116-5p as the most abundant enriched miRNA detected in C-MSC-Exo. Bioinformatics’ analysis shows that miR-7116-5p negatively regulates of protein polyubiquitination. In conclusion, our study demonstrated that intramuscular delivery of C-MSC-Exo after limb ischemia improves blood perfusion, and we identified most abundant miRNAs that are preferentially enriched in C-MSC-Exo.

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Section: Resultsmentioning

confidence: 99%

Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis

Shen

et al. 2018

J. of Cardiovasc. Trans. Res.

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“…The enrichment analysis using FunRich 24 showed that exosomes from bovine colostrum samples were significantly enriched with proteins associated with the innate immune response. Proteins involved in the foremost systemic reaction-like acute phase response (APR) were highly upregulated in the colostrum samples.…”

Section: Discussionmentioning

confidence: 99%

Bovine milk-derived exosomes from colostrum are enriched with proteins implicated in immune response and growth

Samuel

Chisanga

Liem

et al. 2017

Sci Rep

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164

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Exosomes are extracellular vesicles secreted by multiple cell types into the extracellular space. They contain cell-state specific cargos which often reflects the (patho)physiological condition of the cells/organism. Milk contains high amounts of exosomes and it is unclear whether their cargo is altered based on the lactation stage of the organism. Here, we isolated exosomes from bovine milk that were obtained at various stages of lactation and examined the content by quantitative proteomics. Exosomes were isolated by OptiPrep density gradient centrifugation from milk obtained from cow after 24, 48 and 72 h post calving. As control, exosomes were also isolated from cows during mid-lactation period which has been referred to as mature milk (MM). Biochemical and biophysical characterization of exosomes revealed the high abundance of exosomes in colostrum and MM samples. Quantitative proteomics analysis highlighted the change in the proteomic cargo of exosomes based on the lactation state of the cow. Functional enrichment analysis revealed that exosomes from colostrum are significantly enriched with proteins that can potentially regulate the immune response and growth. This study highlights the importance of exosomes in colostrum and hence opens up new avenues to exploit these vesicles in the regulation of the immune response and growth.

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“…Protein list of insulin‐induced and non‐induced LIM1215 EVs generated by Mascot search engine were compared based on Rsc values. Highly abundant proteins found in insulin‐induced sample (more than 2‐fold) were analysed using Cytoscape and FunRich …”

Section: Methodsmentioning

confidence: 99%

Insulin Mediated Activation of PI3K/Akt Signalling Pathway Modifies the Proteomic Cargo of Extracellular Vesicles

Liem

Mathivanan

2017

Proteomics

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Epidemiological studies suggest that diabetes and obesity increases the risk of colorectal cancer (CRC) and lowers the patient survival rate. An important attribute in diabetes and obesity is the presence of high levels of growth factors including insulin in blood which can activate the PI3K/Akt signalling pathway. Dysregulation of PI3K/Akt signalling pathway leads to sustained proliferative signals thereby allowing the cells susceptible to cancer. Extracellular vesicles (EVs), secreted nanovesicles of endocytic origin, are implicated in mediating the transfer of oncogenic cargo in the tumour microenvironment. In this study, CRC cells were treated with insulin to activate PI3K/Akt signaling pathway. Insulin treatment significantly increased the number of EVs secreted by CRC cells. Furthermore, pAkt was exclusively packaged in EVs secreted by PI3K/Akt activated cells. Quantitative proteomics analysis confirmed that the protein cargo of EVs are modified upon activation of PI3K/Akt signaling pathway. Bioinformatics analysis highlighted the enrichment of proteins implicated in cell proliferation in EVs secreted by PI3K/Akt activated cells. Furthermore, incubation of EVs secreted by PI3K/Akt activated cells induced proliferation in recipient CRC cells. These findings suggest that EVs can amplify the signal provided by the growth factors in the tumor microenvironment and hence aid in cancer progression.

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A novel community driven software for functional enrichment analysis of extracellular vesicles data

Cited by 315 publications

References 9 publications

Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis

Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis

Bovine milk-derived exosomes from colostrum are enriched with proteins implicated in immune response and growth

Insulin Mediated Activation of PI3K/Akt Signalling Pathway Modifies the Proteomic Cargo of Extracellular Vesicles

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