The small RNA sequencing data of EcoHIV-infected mouse brain tissue derived extracellular vesicles
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE182743 | GEO | 2021/08/28
REPOSITORIES: GEO
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Project description:Improving embryo implantation rates has become one of the greatest challenges in assisted reproduction techniques. Implantation process requires a synchrony between the development of the embryo and the endometrium, but also, an adequate embryo-endometrial crosstalk. MicroRNAs (miRNAs) and extracellular vesicles (EVs) from endometrial fluid (EF) have been described to be mediators of this communication. Therefore, the molecular analysis of the miRNA content of EF could provide a non-invasive method to recognize an implantative endometrium and consequently improve the implantation rates. In this work, we optimized EF sample collection procedure and performed a comparative analysis of five different methodologies to enrich miRNA content of EF with the purpose of identifying a simple, sensitive, reproducible and non-invasive method that allow the quick identification of an implantative endometrium. Then, we applied the selected methodology in a set of real samples with different implantation outcome. Our results showed that EVs enrichment protocols permit to detect a higher number of miRNAs. In addition, we obtained two predictive models based on three miRNAs that allow us to differentiate between an implantative and non-implantative endometrium. Model 1 (Area under the curve (AUC)=0.93; p-value=0.0033): hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-148b-3p. Model 2 (AUC=0.92; p-value=0.0002): hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-99b-5p. This work supports the feasibility to analyze EVs and EVs-associated miRNAs from a small volume of EF sample and the development of EV-miRNAs based assays as low-invasive tools for the detection of an implantative endometrium.
2022-08-18 | GSE178917 | GEO
Project description:Malignant germ-cell-tumours (GCTs) are characterised by microRNA (miRNA/miR-) dysregulation, with universal over-expression of miR-371~373 and miR-302/367 clusters regardless of patient age, tumour site, or subtype (seminoma/yolk-sac-tumour/embryonal carcinoma). These miRNAs are released into the bloodstream, presumed within extracellular-vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast/endothelial/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next-generation-sequencing was performed on 34 samples, comprising representative malignant GCT cell lines/EVs and controls (testis fibroblast [Hs1.Tes] cell-line/EVs and testis/ovary samples). TME cells received TGCT co-culture, TGCT-derived EVs, and a miRNA overexpression system (miR-371a-OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR-371~373 and miR-302/367 cluster miRNAs were overexpressed in all TGCT cells/subtypes compared with control cells and were highly abundant in TGCT-derived EVs, with miR-371a-3p/miR-371a-5p the most abundant. TGCT co-culture resulted in increased levels of miRNAs from the miR-371~373 and miR-302/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT-derived EVs were internalised by all TME (fibroblast/endothelial/macrophage) cells. TME (fibroblast/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR-371~373 and miR-302/367 miRNA levels, and other generic (eg, miR-205-5p/miR-148-3p) and subtype-specific (seminoma, eg, miR-203a-3p; yolk-sac-tumour, eg, miR-375-3p) miRNAs. MiR-371a-OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially contributing to tumour progression.
2023-09-30 | E-MTAB-13322 | biostudies-arrayexpress
Project description:COPD is a heterogeneous condition without effective disease modifying therapies. Identification of novel inflammatory endotype markers such as extracellular vesicles (EVs), which are important intercellular messengers carrying microRNA (miRNA), may enable earlier diagnosis and disease stratification for a targeted treatment approach. Our aim was to identify differentially expressed EV miRNA in the lungs of COPD patients compared with healthy ex-smokers and determine whether they can help define inflammatory COPD endotypes. EV miRNA were isolated and sequenced from ex-smoking COPD patients and healthy ex-smoker bronchoalveolar lavage fluid. Results were validated with RT-qPCR and compared to differential inflammatory cell counts. Differential expression analysis identified five upregulated miRNA in COPD (miR-223-3p, miR-2110, miR-182-5p, miR-200b-5p and miR-625-3p) and three downregulated miRNA (miR-138-5p, miR-338-3p and miR-204-5p), all with a log2 fold change of >1/-1, FDR<0.05. These miRNAs correlated with disease defining characteristics such as FEF 25-75% (a small airways disease measure) and DLCO % (a surrogate measure of emphysema). Receiver operator curve analysis demonstrated miR-2110, miR-223-3p and miR-182-5p showed excellent combinatory predictive ability (AUC 0.91, p<0.0001) in differentiating between health and mild COPD. Furthermore, miR-223-3p and miR-338-3p correlated with airway eosinophilia and were able to distinguish “pure eosinophilic” COPD from other airway inflammatory subtypes (AUC 0.94 and 0.85 respectively). This is the first study to identify differentially expressed miRNA in COPD bronchoalveolar lavage fluid EVs. These findings suggest specific lung derived EV miRNA are a strong predictor of disease presence even in mild COPD. Furthermore, specific miRNA correlated with inflammatory cell numbers in COPD, and may have a role in defining inflammatory endotypes for future treatment stratification.
2022-12-05 | GSE218571 | GEO
Project description:MiRNAs regulate posttranscriptional gene expression and are widely implicated in the pathogenesis of complex diseases. We aim to elucidate miRNA regulation of the atrial mRNA signatures that associate with AF. This may provide novel mechanistical insights and candidate targets for therapies using miRNA mimics or antimiRs.
We present combined miRNAs-mRNAs sequencing in atrial tissues of patient without AF (n=22), with paroxysmal AF (n=22) and with persistent AF (n=20). MiRNA and mRNA signatures followed an ordinal scale from nonAF to paroxysmal to persistent AF patients. The previously reported mRNA sequencing identified 5228 differentially expressed genes involved in epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving collagens, glycoproteins and proteoglycans. We discovered 103 differentially expressed miRNAs. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. The expression levels of differentially expressed miRNAs were negatively correlated with the expression levels of their predicted target mRNAs. The downregulated miRNAs demonstrated a more profound transcriptome effect than the upregulated miRNAs. Upregulated biological processes enriched in miRNAs targets related to epithelial and endothelial cell migration and glycosaminoglycan biosynthesis, in line with the processes discovered by the mRNA sequencing analysis.
Combined analysis of miRNA and mRNA sequencing uncovered miRNAs with a broad transcriptional effect in human AF. Epithelial to mesenchymal transition and endothelial cell proliferation were processes controlled by downregulated miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p, which in turn may contribute to (myo)fibroblast activation and structural remodeling.\
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Project description:Antiretroviral treatment regimens can effectively control HIV replication and some aspects of disease progression. However, molecular events in end-organ diseases such as central nervous system (CNS) disease are not yet fully understood, and routine eradication of latent reservoirs is not yet in reach. Brain tissue-derived extracellular vesicles (bdEVs) act locally in the source tissue and may indicate molecular mechanisms in HIV CNS pathology. Regulatory RNAs from EVs have emerged as important participants in HIV disease pathogenesis. Using brain tissue and bdEVs from the simian immunodeficiency virus (SIV) model of HIV disease, we profiled messenger RNAs (mRNAs) and microRNAs (miRNAs), seeking to identify possible networks of RNA interaction in SIV infection and neuroinflammation.
2023-09-25 | GSE236656 | GEO
Project description:Hibernating American black bears have significantly different clotting parameters than their active summer counterparts, affording them innate protection against venous thromboembolism (VTE) despite prolonged periods of immobility. Physiologic changes that occur during hibernation are thought to result from differential gene expression, rather than novel genes, and there is increasing evidence miRNAs may play an important role this regulation. We propose that significant differences exist in miRNA expression in the plasma of hibernating black bears compared to their active counter parts (summer), which lead to critical gene regulation responsible for auto-anticoagulation during hibernation. Methods: Blood was collected from 21 American black bears in the Northern Michigan Peninsula in summer 2017 and winter 2018 (11 active, 10 hibernating). Plasma was extracted Results: Fifteen miRNAs were differentially expressed in the plasma of hibernating black bears. Nine miRNAs were significantly downregulated (miR10b-3p, miR-136-3p, miR-181c-5p , miR-200a-3p, miR-200b-5p, miR-200c-3p, miR-320b, miR-320c and miR-320d) and six miRNAs were significantly upregulated (miR-15a-5p, miR-15b-3p, miR-15b-5p, miR-16-5p, miR-92a-3p, miR-150-5p) during hibernation. Twelve miRNAs had no identifiable targets, but miR-200a-3p, miR-200b-5p and miR-200c-3p found to be targets of SERPINC1, the gene responsible for the production of antithrombin (AT). Conclusions: Several miRNAs were differentially expressed in hibernating bears (12). Most importantly miR-200a-3p, miR-200b-5p and miR-200c-3p were all downregulated in hibernation and associated with increased expression of SERPINC1 and production of AT. AT is a powerful anticoagulant and this finding may explain the hibernating black bears ability to achieve auto-anticoagulation and protection from VTE.
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Project description:Bovine mastitis causes changes in the serum exosomal miRNAs expression. Serum samples from healthy dairy cows (n = 7) were compared to those of cows with subclinical (n = 7 ) using small RAN sequencing. Three hundred fifty-five miRNAs (341 known and 14 novel ones) were identified. There were 42 miRNAs up-regulated in serum-derived EVs from cows with subclinical mastitis, including bta-miR-1246, bta-miR-2431-3p, bta-miR-126-3p, bta-miR-29a, etc. The MAPK signaling pathway was the most affected pathway by clinical mastitis. Thus, miRNA alterations in mastitis serum-derived EVs support the potential regulator role of specific miRNAs as exosomal cargo in clinical mastitis physiology.
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2020-08-05 | PXD006350 | Pride
Project description:In this study, we used RNA sequencing to provide a comprehensive overview of the expression profiles of small non-coding transcripts carried by the extracellular vesicles (EVs) derived from human adipose tissue stromal/stem cells (AT-MSCs) and human pluripotent stem cells (hPSCs), both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSC). Small non-coding RNA sequencing from EVs showed that the profile of miRNA expression in PSC follow the profile reported for cell derived miRNA; further, most abundant miRNAs were found to originate from specific miRNA families which are regulating pluripotency, reprograming and differentiation (miR-17–92, mir-200, miR-302/367, miR-371/373, CM19 microRNA cluster). For the AT-MSCs, the highly expressed miRNAs were found to be regulating osteogenesis (mir-let-7/98, miR-10/100, miR-125, miR-196, miR-199, miR-615-3p, mir-22-3p, mir-24-3p, mir-27a-3p, mir-193b-5p, mir-195-3p). Additionally, abundant small nuclear and nucleolar RNA were detected in PSCs, whereas Y- and tRNA were found in AT-MSCs. Identification of EV-miRNA and non-coding RNA signatures released by these stem cells will provide clues towards understanding their role in intracellular communications, and well as their roles in maintaining the stem cell niche.
2018-10-30 | GSE113868 | GEO
Project description:Secreted microRNAs (miRNAs) enclosed within extracellular vesicles (EVs) play a pivotal role in intercellular communication by regulating recipient cell gene expression and affecting target cell function. Here, we report the isolation of three distinct EV subtypes from the human colon carcinoma cell line LIM1863--shed microvesicles (sMVs) and two exosome populations (immunoaffinity isolated A33-exosomes and EpCAM-exosomes). Deep sequencing of miRNA libraries prepared from parental LIM1863 cells/derived EV subtype RNA yielded 254 miRNA identifications, of which 63 are selectively enriched in the EVs--miR-19a/b-3p, miR-378a/c/d, and miR-577 and members of the let-7 and miR-8 families being the most prominent. Let-7a-3p*, let-7f-1-3p*, miR-451a, miR-574-5p*, miR-4454 and miR-7641 are common to all EV subtypes, and 6 miRNAs (miR-320a/b/c/d, miR-221-3p, and miR-200c-3p) discern LIM1863 exosomes from sMVs; miR-98-5p was selectively represented only in sMVs. Notably, A33-Exos contained the largest number (32) of exclusively-enriched miRNAs; 14 of these miRNAs have not been reported in the context of CRC tissue/biofluid analyses and warrant further examination as potential diagnostic markers of CRC. Surprisingly, miRNA passenger strands (star miRNAs) for miR-3613-3p*, -362-3p*, -625-3p*, -6842-3p* were the dominant strand in A33-Exos, the converse to that observed in parental cells. This finding suggests miRNA biogenesis may be interlinked with endosomal/exosomal processing. This work was supported by National Health and Medical Research Council of Australia (NHMRC) program grant #487922.
2016-10-12 | GSE87839 | GEO