Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)
TISSUE(S): Blood Plasma
DISEASE(S): Multiple Sclerosis
SUBMITTER: 
Cory Willis
LAB HEAD: Stephen J. Crocker
PROVIDER: PXD013630 | Pride | 2019-09-27
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| F502502.dat | Other | |||
| F502503.dat | Other | |||
| F502504.dat | Other | |||
| F502505.dat | Other | |||
| F502506.dat | Other |
Items per page: 5 1 - 5 of 26 |
Similar Datasets
Project description:Extracellular vesicles isolated from the conditioned media of short, long-term, and rapamycin treated long-term cultured astrocytes were subjected to proteomic analysis to determine the how the EV proteome changes following long-term culture.
2020-05-27 | PXD017058 | Pride
Project description:Purified mitochondrial ATP synthase has been shown to form Ca2+-activated, large conductance channel activity similar to that of mitochondrial megachannel (MMC) or mitochondrial permeability transition pore (mPTP) but the oligomeric state required for channel formation is being debated. We reconstitute purified monomeric ATP synthase from porcine heart mitochondria into small unilamellar vesicles (SUVs) with the lipid composition of mitochondrial inner membrane and analyze its oligomeric state by electron cryomicroscopy. The cryo-EM density map reveals the presence of a single ATP synthase monomer with no density seen for a second molecule tilted at an 86o angle relative to the first. We show that this preparation of SUV-reconstituted ATP synthase monomers, when fused into giant unilamellar vesicles (GUVs), forms voltage-gated and Ca2+-activated channels with the key features of mPTP. Based on our findings we conclude that the ATP synthase monomer is sufficient, and dimer formation is not required, for mPTP activity.
2020-01-13 | PXD016255 | Pride
Project description:Dysregulated expression of oncogenic splicing factors (SFs) occurs in human tumors in part through alterations in splicing of poison exons (PE), highly conserved exons that trigger RNA degradation. TRA2β is one such SF that undergoes PE suppression in tumor cells. Therefore, manipulation of TRA2β-PE can be a promising therapeutic strategy for cancer. Here, we demonstrate that low TRA2β-PE inclusion correlates with decreased patient survival across multiple tumor types. TRA2β-PE-targeting antisense oligonucleotides (ASOs) induce anti-cancer phenotypes and widespread transcriptomic alterations in cell culture models by causing both TRA2β protein knockdown and upregulation of TRA2β-PE-containing transcripts, which act as long-noncoding RNAs (lncRNAs) to sequester nuclear proteins. Finally, we demonstrate efficacy of TRA2β-PE-targeting ASOs in preclinical 3D organoid and in vivo patient-derived xenograft models. Together, this demonstrates that oncogenic SFs can be drugged using PE-targeting ASOs and elucidates a mechanism by which the TRA2β-PE acts both as a regulator of TRA2β protein expression and as a lncRNA that controls cancer cell growth.
2024-12-20 | PXD042941 | Pride
Project description:Previously we have demonstrated that inactivation of retinoic acid receptor beta (Rarb) in the mouse results in a protective effect against ErbB2-induced mammary gland tumorigenesis although Rarb has been reported as a tumor suppressor before. In the current study, we further confirmed that ablation of Rarb has a very similar impact on Wnt1-induced mammary gland tumorigenesis as those on ErbB2-induced mammary gland tumorigenesis. Nevertheless, the mechanisms by which Rarb confers its effects on tumor progression is quite different although both involving in tumor microenvironment (TME) remodeling. In the Wnt1 tumors, ectopic wnt1 produced by malignant luminal cells activates nearby stromal cells by a paracrine manner. In return, the stromal cells secreted IGF1 to regulate the growth of tumor cells. There is a need of Rarb expression in this interaction. Deletion of Rarb inhibits both wnt1/β-catenin signaling and IGF1/Akt axis in the myoepithelial tumor cells which results in the suppression of epithelial-mesenchymal transition (EMT) in these tumors. Since wnt1 tumors resemble basal-like breast cancer with a poor clinical prognosis in which EMT is one of the most important way for tumor cells to survive against standard treatment and to go to metastasis, we propose that (1) the stromal gene expression signature of Rarb ablation in wnt1 tumors could have some clinical value in predicting the breast cancer outcome; and (2) Rarb antagonist might be a potential therapeutic strategy in EMT-driven aggressive cancers such as basal-like breast cancer. Laser capture microdissection (LCM) was performed to separate the mammary tumor samples into epithelial cell compartment and stromal cell compartment. Transcriptional profiling of the two compartments were investigated by microarray analysis.
2014-10-23 | E-GEOD-56391 | biostudies-arrayexpress
Project description:Background: Epithelial-stromal crosstalk plays a critical role in invasive breast cancer (IBC) pathogenesis; however, little is known on a systems level about how epithelial-stromal interactions evolve during carcinogenesis. Results: We develop a framework for building genome-wide epithelial-stromal co-expression networks composed of pairwise co-expression relationships between mRNA levels of genes expressed in the epithelium and stroma across a population of patients. We apply this method to laser capture micro-dissection expression profiling datasets in the setting of breast carcinogenesis. Our analysis shows that epithelial-stromal co-expression networks undergo extensive re-wiring during carcinogenesis, with the emergence of distinct network hubs in normal breast, ER-positive IBC, and ER-negative IBC, and the emergence of distinct patterns of functional network enrichment. In contrast to normal breast, the strongest epithelial-stromal co-expression relationships in IBC mostly represent self-loops, in which the same gene is co-expressed in epithelial and stromal regions. We validate this observation using an independent laser capture micro-dissection dataset and confirm that self-loop interactions are significantly increased in cancer by performing computational image analysis of epithelial and stromal protein expression using images from the Human Protein Atlas. Conclusions: Epithelial-stromal co-expression network analysis represents a new approach for systems-level analyses of spatially-localized transcriptomic data. The analysis provides new biological insights into the re-wiring of epithelial-stromal co-expression networks and the emergence of epithelial-stromal co-expression self-loops in breast cancer. The approach may facilitate the development of new diagnostics and therapeutics targeting epithelial-stromal interactions in cancer. 36 flash-frozen human primary breast cancer samples were subjected to laser capture microdissection to separately isolate matched tumor epithelial and tumor-associated stromal components. RNA was isolated, subjected to 2 rounds of amplification, and hybridized on Agilent 4x44K microarrays along with a common reference (single round-amplified commercially obtained Universal Human Reference RNA) in a dyeswap design. For two samples of tumor-associated stroma, a second technical replicate was performed. Samples were labelled as ER-positive based on ESR1 gene expression levels in the tumor epithelium, using univariate Gaussian mixture model-based clustering via the mclust package in R.
2015-05-12 | E-GEOD-68744 | biostudies-arrayexpress
Project description:Ibrutinib,a novel Bruton'styrosine kinase inhibitor, demonstrated high response rates in B-cell lymphomas but a growing number of ibrutinib treated patients relapse with resistance, fulminant progression and accelerated mortality. Using chemical proteomics and a high-throughput ex vivo assay in a reconstructed tumor microenvironment (TME), we determined the molecular basis for ibrutinib activity and mechanism of acquired ibrutinib resistance. Reciprocal activation of PI3K-AKT-mTOR and integrin β1 signaling were identified as a signaling hub of kinome for ibrutinib resistance, resulting in enforced TME-lymphoma interactions, promoting mantle cell lymphoma (MCL) growth and drug resistance. Combinatorial disruption of BCR signaling and ibrutinib resistance associated pathways led to release of MCL cells from TME, reversal of drugresistance and enhanced anti-MCL activity in murine and patient-derived xenograft models. This study integrated TME-mediated de-novo and acquired drug resistance mechanisms and provides the rationale for novel combination therapeutic strategy against MCL and other B cell malignancies.
2018-10-26 | PXD005734 | Pride
Project description:The COVID-19 pandemic is arguably the most important global threat to humankind that the world has seen in the 21st century. Since the initial outbreak of SARS-CoV-2 in 2019, the virus genome is continuously mutating that may affect virus characteristics such as infectivity, transmission, and pathogenicity. We recently found that two consecutive amino acid mutations R203K and G204R in the nucleocapsid (N) protein, are linked with higher viral load and severity in COVID-19 patients. Here, we performed comparative total proteomic analysis of HEK293T (stably expressing ACE2/TMPRSS2) cell lines infected with wildtype (WT) VLP, KR-mutant (KR) VLP with two mutations R203K/G204R in the nucleocapsid protein, and two additional controls D614G-KR (containing both R203K/G204R and spike D614G mutations) and D614G (only spike D614G mutation). Our data reveal enhanced expression of immune response proteins in KR VLP infected cells.
2023-04-15 | PXD034557 | Pride
Project description:The analysis identifies genes which are dependent on USP22 expression in murine HER2-driven murine mammary carcinomas.
2021-05-26 | E-MTAB-9331 | biostudies-arrayexpress
Project description:Endothelial cells play many important role during development and development of diseases. Endothelial dysfunction which is commonly seen in diabetes patients is thought to be one of the first step that leads to adverse events such as retinopathy, nephropathy, and atherosclerosis. To examine to which extent TGF-beta signaling contributes to insulin-induced transcriptional responses we performed this RNAseq on Human umbilical vein endothelial cells.
2019-01-15 | E-MTAB-6841 | biostudies-arrayexpress
Project description:Integrins are a major class of heterodimeric adhesion receptors composed of an a and b subunit that mediate cell adhesion to the extracellular matrix (ECM). The extracellular matrix protein fibronectin is important for early vertebrate development, and Integrin a5b1 and aVb3 are the two primary fibronectin receptors. To better define the integrin – ECM protein network at 10-13 somite stage of zebrafish development, we performed co-immunoprecipitation and Mass Spectrometry (MS) based proteomics using FLAG-tagged Integrin a5, aV, and aVb3 expressed in maternal zygotic a5 mutant (MZa5-/-) embryos. We found that Integrin a5b1 and aVb1 are the functional fibronectin receptors, whereas Integrin aVb3 displayed low affinity to both fibronectins (Fn1a and Fn1b). In addition, basement membrane ligands Laminins (lama1, lamb1a, lamc1) are roughly equal in all three datasets while Thrombospondins (thbs3b, thbs4b) and cartilage oligomeric matrix protein (comp/thbs5) are found exclusively in the aV dataset. Our results suggest a diverse role of aV class integrins in ECM protein recruitment.
2021-09-10 | PXD024665 | Pride