The role of extracellular vesicle miRNAs and tRNAs in synovial fibroblast senescence
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE200330 | GEO | 2022/08/31
REPOSITORIES: GEO
Similar Datasets
Project description:We studied microRNA expression levels from serum of postmenopausal women with osteoporosis by investigating the anti-osteoporotic treatment denosumab for a period of 2 years in a longitudinal study. Serum RNA was extracted and subject to small RNA sequencing on an Illumina HiSeqV4 SR50 using 50bp, single end reads. After mapping against GRCh38.p12 provided by Ensembl and miRBase v22.1 differential expression analysis was undertaken with edgeRv3.28 using a quasi-likelihood negative binomial generalized log-linear model. We identified a panel of altered small non-coding RNAs between 3 different time points for all patients.
2023-12-31 | GSE206540 | GEO
Project description:We studied extracellular vesicles (EVs) from plasma and synovial fluid in an in vivo model of equine osteoarthritis by investigating longitudinal samples. EVs were isolated using size exclusion chromatography from plasma and synovial fluid of four horses subjected to an osteochondral fragment model of osteoarthritis at 0, 10, 35, 42, 49, 56, 63 days with relevant controls.EV RNA was extracted and subject to small RNA sequencing on an Illumina NovaSeq SP using 100bp, single end reads. After mapping against EquCab.3.0 and miRBase v22.1 differential expression analysis was undertaken with edgeRv3.28 using a quasi-likelihood negative binomial generalized log-linear model. We identified a panel of altered small non-coding RNAs.
2023-12-31 | GSE195807 | GEO
Project description:We studied microRNA expression levels from serum and ulna bone in an in vivo model of type II diabetes (ZDF rats) by investigating different anti-osteoporotic treatments (anti-sclerostin, PTH and insulin). Serum and ulna bone RNA were extracted and subject to small RNA sequencing on an Illumina NextSeq550 SR75 High using 75bp, single end reads. After mapping against Rnor.6.0 provided by Ensembl and miRBase v22.1 differential expression analysis was undertaken with edgeRv3.32 using a quasi-likelihood negative binomial generalized log-linear model. We identified a panel of altered small non-coding RNAs.
2022-06-27 | GSE201231 | GEO
Project description:In arthritis, synovial fibroblast (SF) senescence is linked to the activation of a pro-inflammatory phenotype contributing to chronic arthritis pathogenesis. Additionally, senescent cells accumulate in ageing tissues further promoting ageing and inflammation. These cells have dysregulated mitochondrial function and metabolism, limited tissue regeneration, produce reactive oxygen species (ROS) and secrete bioactive molecules, including pro-inflammatory cytokines, chemokines and matrix-remodelling enzymes known as SASP (senescence-associated secretory phenotype). In vitro, senescent cells can induce a senescent phenotype in surrounding bystander cells. Interestingly, extracellular vesicles (EVs) have critical roles in cellular senescence and ageing and are mediators in intercellular communication. We hypothesize that senescent cells in osteoarthritic SFs induce senescence and/or a proinflammatory phenotype in non-senescent osteoarthritic SFs, mediated through EV cargo.
2022-10-15 | PXD032757 | Pride
Project description:The current study examined the association between genotype and resistance training-induced changes in dual energy x-ray absorptiometry (DXA) derived lean soft-tissue mass (LSTM) and skeletal muscle fiber cross-sectional area (fCSA). Over 315,000 genetic polymorphisms were interrogated using DNA microarrays. Genome-wide association studies (GWAS) were performed to identify novel targets to reveal associations with PRE- to POST-training change scores in mean LSTM and fCSA. The first GWAS indicated no single nucleotide polymorphisms (SNP) associated with DXA derived LSTM. The second GWAS indicated two SNPs associated with changes in mean fCSA. While the first target identified (chr2:205936849 [GRCh38.p12]) was not annotated the second target identified (chr7:41971865 [GRCh38.p12]) was identified as an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype.
2022-01-03 | GSE169300 | GEO
Project description:Whole genome sequencing (WGS) of tongue cancer samples and cell line was performed to identify the fusion gene translocation breakpoint. WGS raw data was aligned to human reference genome (GRCh38.p12) using BWA-MEM (v0.7.17). The BAM files generated were further analysed using SvABA (v1.1.3) tool to identify translocation breakpoints. The translocation breakpoints were annotated using custom scripts, using the reference GENCODE GTF (v30). The fusion breakpoints identified in the SvABA analysis were additionally confirmed using MANTA tool (v1.6.0).
2024-02-17 | E-MTAB-12534 | biostudies-arrayexpress
Project description:Cellular senescence prevents the proliferation of cells at risk for neoplastic transformation. However, the altered secretome of senescent cells can promote the growth of the surrounding cancer cells. Although extracellular vesicles (EVs) have emerged as new players in intercellular communication, their role in the function of senescent cell secretome has been largely unexplored. Here, we show that exosome-like small EVs (sEVs) are important mediators of the pro-tumorigenic function of senescent cells. sEV-associated EphA2 secreted from senescent cells binds to ephrin-A1 that is highly expressed in several types of cancer cells and promotes cell proliferation through EphA2/ephrin-A1 reverse signalling. sEV sorting of EphA2 is increased in senescent cells due to its enhanced phosphorylation resulting from oxidative inactivation of PTP1B phosphatase. Our results demonstrate a novel mechanism of reactive oxygen species (ROS)-regulated cargo sorting into sEVs, which is critical for the potentially deleterious growth-promoting effect of the senescent cell secretome.
2017-02-28 | GSE81373 | GEO
Project description:Senescent cells are beneficial for repairing acute tissue damage but are harmful when they accumulate in tissues, as occurs with advancing age. Senescence-associated extracellular vesicles (S-EVs) can mediate cell-to-cell communication and export intracellular content to the microenvironment of aging tissues. Here, we studied the uptake of EVs from senescent cells (S-EVs) relative to proliferating cells (P-EVs). Interestingly, P-EVs were readily taken up by other proliferating cells (fibroblasts and cervical cancer cells) while S-EVs were not; by contrast, macrophages selectively engulfed all EVs (P-EVs, S-EVs). We thus investigated the surface proteome (surfaceome) of P-EVs relative to S-EVs derived from cells that had reached senescence via replicative exhaustion, exposure to ionizing radiation, or treatment with etoposide. We discovered that relative to P-EVs, S-EVs from all senescence models were enriched in proteins DPP4, ANXA1, ANXA6, S10AB, AT1A1, and EPHB2. Among them, DPP4 was found to dictate selective uptake by proliferating cells, as ectopic overexpression of DPP4 in HeLa cells rendered DPP-expressing EVs that were no longer taken up by other proliferating cells. We propose that DPP4 on the surface of S-EVs makes these EVs refractory to internalization by proliferating cells, advancing our knowledge of the impact of senescent cells in aging-associated processes.
2022-10-09 | MSV000090503 | MassIVE
Project description:To identify cellular senescence markers using senescent fibroblast-derived extracellular vesicles (EVs), we collected small EVs by three different methods: size exclusion chromatography (SEC), affinity column for phosphatidylserine (PS), and immunoprecipitation (IP) using antibodies against tetraspanin proteins (CD9, CD63 and CD81), from young and senescent fibroblasts to proteomic analysis. In addition, small EVs were collected from culture supernatants of cells derived from patients with Werner's syndrome, a known Progeria, and healthy individuals, and subjected to proteomic analysis.
2023-10-29 | PXD037822 | JPOST Repository
Project description:Atherosclerosis represents an age-related disease, which remains one of the leading cause of deaths in developed countries. It begins with a local deposition of lipid in the innermost part of the artery – intima. Thereafter a number of immune cells are attracted and infiltrate into the artery wall, where, together with endothelia and smooth muscle cells, form an atherosclerotic plaque (Libby, 2008). Thus, atherosclerosis is considered as an inflammatory disease, characterized by intense immunological activity (Libby P, 2012). One of the main risk factor for atherosclerosis is aging. It was demonstrated that there is an accumulation of senescent cells within atherosclerotic plaque (..). Accordingly, vascular smooth muscle cells (VSMCs) derived from the lesion demonstrate a phenotype characteristic for senescent cells: diminished proliferative potential, shorter telomeres, increased number of DNA damage and upregulation of SA-β-gal activity (Gorenne, 2006; Matthes, 2006, Mahomoudi, 2008). Accumulation of senescent VSMCs within the area of plaque development promotes its instability due to lack of proliferation and impaired production of extracellular matrix, both leading to weakening of fibrous cap (Gorenne, 2006). This has been further confirmed by the observation, that elimination of senescent cells in the atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr-/-) mice slowed down the disease progression (27789842). One of the most important feature of senescent cells, that has the biggest impact on tissue microenvironment, is their ability to secrete a number of cytokines, chemokines, matrix metalloproteinases and growth factors collectively known as the Senescence Associated Secretory Phenotype (SASP) (20078217, 28165648). Apart from soluble factors, senescent cells secret also an increased number of extracellular vesicles (EVs), research of which has only recently begun (32461143). EVs are small membranous vesicles that can be categorized based on their size and origin, into: exosomes, microvesicles and apoptotic bodies. EVs play crucial role as carriers of proteins, different types of RNA and DNA, lipids and metabolites that, take part in intercellular communication (23420871). They were shown to participate in many physiological but also pathological conditions. Studies performed over the last decade proved that EVs affect atherosclerosis progression at different stages by several distinct mechanisms (as reviewed by Knokhot, 2020, 33261815). The increased concentrations of EVs have been found in plasma of patients suffering from cardiovascular diseases as well as in atherosclerotic plaque itself (Yin, 2015, 26142082; Rautou, 2011, 21852557). However, the role of EVs derived from senescent cells in atherosclerosis, particularly in the context of the plaque development, remains unknown. The functioning of immune cells within atherosclerotic plaque is modulated by local milieu. Thus, senescent cells present in the lesion can influence plaque development by non-cell autonomous mechanism. Indeed, recently it was demonstrated that SASP factors secreted by senescent VSMCs promote recruitment of monocytes, induce expression of adhesion receptors on endothelial cells and activate adjacent normal VSMCs, promoting inflammation in the plaque (Gardner, 2015). However, the role of EVs in this context has not been studied. Thus, we have undertaken research aimed at investigating the role of senescent cell derived EVs on immune cells activity. To this end, we isolated and characterized the EVs secreted by human VSMCs undergoing senescence. We performed unbiased quantitative proteomic analysis of both soluble and insoluble SASP components. Moreover, we analyzed the influence of EVs derived from senescent and non-senescent cells on T lymphocytes and monocytes. Altogether our studies revealed that EVs produced by senescent VSMCs strengthen inflammatory response of the immune cells, what would have a tremendous significance in atherosclerotic plaque development.
2022-09-08 | PXD030955 | Pride