Small RNA sequencing of small extracellular vesicles secreted by nonsenescent vs. senescent human umbilical cord mesenchymal stem cells
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PROVIDER: PRJNA801605 | ENA |
REPOSITORIES: ENA
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Project description:We report small RNA sequencing technology for high-throughput profiling of microRNA content within small extracellular vesicles isolated from nonsenescent and senescent human umbilical cord mesenchymal stem cells (hUCMSCs)
2022-01-31 | GSE195634 | GEO
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:We report small RNA sequencing technology for high-throughput profiling of microRNA content within small extracellular vesicles isolated from nonsenescent and senescent human dermal fibroblasts.
2021-09-16 | GSE184084 | GEO
Project description:Mesenchymal stromal cells (MSCs) are multipotent progenitors that can be isolated from different sources, such as the bone marrow, adipose tissue and umbilical cord. The therapeutic potential of MSCs is related to a plethora of immunomodulatory, anti-inflammatory and pro-repair actions, which are at least partially dependent on their secretome. Among the components of MSCs' secretome, EVs have received considerable attention because MSC-EVs exert similar therapeutic properties as their parent cells. Among the different MSC sources for EV production, human umbilical cord MSCs (hUCMSCs) show advantages such as tissue availability, high proliferative profile of the cells and potential beneficial therapeutic effects in a variety of different diseases, such as stroke This study aimed to provide novel insights for future hUCMSC-EVs research and treatment selection. We investigated the influence of the culture and harvesting conditions on the EV proteomic profile, productivity, surface markers expression and evaluated their in vivo biodistribution and toxicity.
2024-05-04 | PXD038850 | Pride
Project description:Although long thought to act cell autonomously, mutant KRAS colorectal cancer (CRC) cells release protein-laden exosomes that can alter the tumor microenvironment. We have previously shown that mutant KRAS induces EGFR-ligand trafficking to exosomes and drastically alters exosomal protein contents, leading to activities that contribute to neoplastic growth. We have performed small library RNAseq analysis on cells and matched exosomes from isogenic CRC cell lines differing only in KRAS status to determine whether mutant KRAS regulates the composition of secreted small RNAs. Exosomal small RNA profiles were distinct from cellular profiles, with principle component analysis showing clusters of mutant KRAS cell-derived exosomes distinct from wild type KRAS cell-derived exosomes. Secreted RNA species encompassed several different classes of small RNAs, including ribosomal and tRNA fragments, as well as mature miRNA sequences. miR-10b, was selectively increased in wild type KRAS-derived exosomes, whereas miR-100 was selectively increased in mutant KRAS-derived exosomes. Ceramide inhibition resulted in accumulation of miR-100 in mutant KRAS cells, suggesting KRAS-dependent miRNA export. In Transwell cell culture experiments, mutant, but not wild type, KRAS donor cells conferred miR-100-mediated target repression in wild type KRAS recipient cells miRNAseq deep sequencing for both cell and exosome mirnas of Dks-8, DLD-1, and DKO-1 cell lines. The DKs-8 line contains a wild type KRAS alleles, the DLD-1 line contains both wild type and mutant (G13D) KRAS alleles, and the DKO-1 line contains only a mutant KRAS allele.
2015-08-28 | E-GEOD-67004 | biostudies-arrayexpress
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
Project description:Although long thought to act cell autonomously, mutant KRAS colorectal cancer (CRC) cells release protein-laden exosomes that can alter the tumor microenvironment. We have previously shown that mutant KRAS induces EGFR-ligand trafficking to exosomes and drastically alters exosomal protein contents, leading to activities that contribute to neoplastic growth. We have performed small library RNAseq analysis on cells and matched exosomes from isogenic CRC cell lines differing only in KRAS status to determine whether mutant KRAS regulates the composition of secreted small RNAs. Exosomal small RNA profiles were distinct from cellular profiles, with principle component analysis showing clusters of mutant KRAS cell-derived exosomes distinct from wild type KRAS cell-derived exosomes. Secreted RNA species encompassed several different classes of small RNAs, including ribosomal and tRNA fragments, as well as mature miRNA sequences. miR-10b, was selectively increased in wild type KRAS-derived exosomes, whereas miR-100 was selectively increased in mutant KRAS-derived exosomes. Ceramide inhibition resulted in accumulation of miR-100 in mutant KRAS cells, suggesting KRAS-dependent miRNA export. In Transwell cell culture experiments, mutant, but not wild type, KRAS donor cells conferred miR-100-mediated target repression in wild type KRAS recipient cells
2015-08-28 | GSE67004 | GEO
Project description: Not available
| S-EPMC5467215 | biostudies-literature
Project description:Osteolineage cells represent one of the critical bone marrow niche components that support maintenance of hematopoietic stem and progenitor cells (HSPCs). Recent studies demonstrate that extracellular vesicles (EVs) regulate stem cell development via horizontal transfer of bioactive cargo, including microRNAs (miRNAs). Here, we characterize the miRNA profile of EVs secreted by human osteoblasts and study their biological effect of on human umbilical cord blood-derived CD34+ HSPCs by sequencing, gene expression and biochemical analyses. Using next-generation sequencing we show that osteoblast-derived EVs contain highly abundant miRNAs specifically enriched in EVs, including critical regulators of hematopoietic proliferation (e.g., miR-29a). EV treatment of CD34+ HSPCs alters the expression of candidate miRNA targets, such as HBP1, BCL2 and PTEN. Furthermore, EVs enhance proliferation of CD34+ cells and their immature subsets in growth factor-driven ex vivo expansion cultures. Importantly, EV-expanded cells retain their differentiation capacity in vitro and show successful engraftment in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice in vivo. These discoveries reveal a novel osteoblast-derived EV-mediated mechanism for regulation of HSPC proliferation and warrant consideration of EV-miRNAs for the development of expansion strategies to treat hematological disorders.
2016-10-05 | E-MTAB-4560 | biostudies-arrayexpress
Project description:There were no studies about gene expression of umbilical cord tissue before. We performed this study to identify the gene expression of umbilical cord tissue.
2016-11-22 | GSE75642 | GEO