Extracellular Vesicle exposure induced DNA methylation changes in normal Hematopoietic Stem Progenitor Cells: the first proof of concept in Acute Myeloid Leukemia model
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE269215 | GEO | 2025/03/31
REPOSITORIES: GEO
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Project description:Osteolineage cell-derived extracellular vesicles (EVs) play a regulatory role in hematopoiesis and have been shown to promote the ex vivo expansion of human hematopoietic stem and progenitor cells (HSPCs). Here, we demonstrate that EVs from different human osteolineage sources do not have the same HSPC expansion promoting potential. Comparison of stimulatory and non-stimulatory osteolineage EVs by next-generation sequencing and mass spectrometry analyses revealed distinct microRNA (miRNA) and protein signatures identifying EV-derived candidate regulators of ex vivo HSPC expansion. Accordingly, the treatment of umbilical cord blood-derived CD34+ HSPCs with stimulatory EVs altered HSPC transcriptome, including genes with known roles in cell proliferation. An integrative bioinformatics approach, which connects the HSPC gene expression data with the candidate cargo in stimulatory EVs, delineated the potentially targeted biological functions and pathways during hematopoietic cell expansion and development. In conclusion, our study gives novel insights into the complex biological role of EVs in osteolineage cell-HSPC crosstalk and promotes the utility of EVs and their cargo as therapeutic agents in regenerative medicine.
2020-03-01 | GSE143613 | GEO
Project description:Osteolineage cell-derived extracellular vesicles (EVs) play a regulatory role in hematopoiesis and have been shown to promote the ex vivo expansion of human hematopoietic stem and progenitor cells (HSPCs). Here, we demonstrate that EVs from different human osteolineage sources do not have the same HSPC expansion promoting potential. Comparison of stimulatory and non-stimulatory osteolineage EVs by next-generation sequencing and mass spectrometry analyses revealed distinct microRNA (miRNA) and protein signatures identifying EV-derived candidate regulators of ex vivo HSPC expansion. Accordingly, the treatment of umbilical cord blood-derived CD34+ HSPCs with stimulatory EVs altered HSPC transcriptome, including genes with known roles in cell proliferation. An integrative bioinformatics approach, which connects the HSPC gene expression data with the candidate cargo in stimulatory EVs, delineated the potentially targeted biological functions and pathways during hematopoietic cell expansion and development. In conclusion, our study gives novel insights into the complex biological role of EVs in osteolineage cell-HSPC crosstalk and promotes the utility of EVs and their cargo as therapeutic agents in regenerative medicine.
2020-02-13 | GSE145178 | GEO
Project description:EVs are known to play an important role in communication between bone cells. However, few studies have been carried out on EVs derived from osteocytes. The main aim of this project was to collect, characterize and evaluate the potential osteogenic properties of EVs derived from bone, composed of 95% osteocytes. Two subpopulations of EVs, large EVs (lEVs) and small EVs (sEVs), were isolated by differential centrifugation from Swiss male mouse long bone cortices and were characterized from a physico-chemical and functional point of view. Identification of protein and miRNA cargos associated with lEVs and sEVs was carried out by proteomics and small RNA-Seq respectively.
2025-09-30 | GSE250170 | GEO
Project description:Osteolineage cell-derived extracellular vesicles (EVs) play a regulatory role in hematopoiesis and have been shown to promote the ex vivo expansion of human hematopoietic stem and progenitor cells (HSPCs). Here, we demonstrate that EVs from different human osteolineage sources do not have the same HSPC expansion promoting potential. Comparison of stimulatory and non-stimulatory osteolineage EVs by next-generation sequencing and mass spectrometry analyses revealed distinct microRNA and protein signatures identifying EV-derived candidate regulators of ex vivo HSPC expansion. Accordingly, the treatment of umbilical cord blood-derived CD34+ HSPCs with stimulatory EVs altered HSPC transcriptome, including genes with known roles in cell proliferation. An integrative bioinformatics approach, which connects the HSPC gene expression data with the candidate cargo in stimulatory EVs, delineated the potentially targeted biological functions and pathways during hematopoietic cell expansion and development. In conclusion, our study gives novel insights into the complex biological role of EVs in osteolineage cell-HSPC crosstalk and promotes the utility of EVs and their cargo as therapeutic agents in regenerative medicine.
2020-02-28 | PXD017172 | Pride
Project description:The present study revealed that CD63+ and MHC-1+ EVs from CD47-deficient T cells are enriched in small non-coding RNAs relative to the respective EVs from WT cells. CD47-deficient T cells secrete more CD63+ and MHC-1+ EVs, but MHC-1+ EVs are selectively taken up more by human umbilical vein endothelial cells. Microarray analysis of endothelial cells treated with CD63+ or MHC-1+ EVs showed surface marker- and CD47-dependent changes in gene expression in the target cells. Gene set enrichment analysis identified CD47-dependent and surface marker-dependent effects of T cell EVs on VEGF and inflammatory signaling, cell cycle, and on lipid and cholesterol metabolism. Thus, subsets of T cell EVs differentially regulate endothelial cell metabolism and inflammatory and angiogenic responses.
2022-10-07 | GSE185918 | GEO
Project description:Comparative RNA profiling between tumor cells and their secreted extracellular vesicles. Results revealed enrichment in genes involved in cellular migration and metastasis in extracellular vesicles, in agreement with their role as mediators of tumor progression. Mice were orthotoplically transplanted with MDA-MB-231 Breast Adenocarcinoma cells. Cells and extracellular vesicles (EVs) from the resulting tumors were isolated. EVs were characterized by electron microscopy and Nanoparticle Tracking Analysis before total RNA isolation for comparative analysis with cellular RNA. Three biological replicates were analyzed in (technical) duplicate.
2015-03-05 | E-GEOD-66488 | biostudies-arrayexpress
Project description:Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we investigate whether primary human bone marrow derived mesenchymal stromal cells (BMSC) EVs isolated from two different origins, fetal (fEV) and adult (aEV) tissue, can increase the relative low number of HSPCs found in umbilical cord blood (UCB) and which EV-derived components are responsible for ex vivo HSPC expansion. Interestingly, aEVs but and to a lesser extent fEVs, showed supportive ex vivo expansion capacity of UCB-HSPCs. Taking advantage of the two BMSC sources with different supportive effects, we analyzed the EV cargo and investigated how gene expression is modulated in HSPCs after incubation with aEVs and fEVs. Proteomics analyses of the protein cargo composition of the supportive aEV versus the less-supportive fEV identified 90% of the Top100 exosome proteins present in the ExoCarta database. Gene Ontology (GO) analyses illustrated that the proteins overrepresented in aEVs were annotated to oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport, or protein folding. In contrast, the proteins overrepresented in fEVs were annotated to extracellular matrix organization positive regulation of cell migration or transforming growth factor beta receptor (TGFBR) signaling pathway. Small RNA sequencing identified different molecular signatures between aEVs and fEVs. Interestingly, the microRNA cluster miR-99b/let-7e/miR-125a, previously identified to increase the number of HSPCs by targeting multiple pro-apoptotic genes, was highly and significantly enriched in aEVs. Although we identified significant differences in the supportive effects of aEVs and fEVs, RNAseq analyses of the 24hrs treated HSPCs indicated that a limited set of genes was differentially regulated when compared to cells that were treated with cytokines only. Together, our study provides novel insights into the complex biological role of EVs and illustrates that aEVs and fEVs differentially support ex vivo expansion capacity of UCB-HSPCs. Together opening new means for the application of EVs in the discovery of therapeutics for more efficient ex vivo HSPC expansion.
2021-02-10 | GSE165323 | GEO
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:Extracellular vesicles (EVs) are mammalian cell-derived nano-scale structures enclosed by a lipid bilayer that were previously considered to be cell debris with little biological value. However, EVs are now recognized to possess biological function, acting as a packaging, transport and delivery mechanism by which functional molecules (i.e. miRNAs) can be transferred to target cells over some distance. To examine the miRNA from keratinocyte-derived EVs, we isolated three distinct populations of EVs from both HaCaT and primary human keratinocytes (PKCs) and characterized their biophysical, biochemical and functional features by using microscopy, immunoblotting, nanoparticle tracking, and next generation sequencing. We identified 1048; 906; and, 704 miRNAs, respectively, in apoptotic bodies (APs), microvesicles (MVs) and exosomes (EXs) released from HaCaT, and 608; 506; and, 622 miRNAs in APs, MVs and EXs released from PKCs. In which, there were 623 and 437 identified miRNAs common to three HaCaT-derived EVs and PKC-derived EVs, respectively. In addition, we found hundreds of exosomal miRNAs that were previously un-reported and that differences in the abundance levels of the identified EV miRNAs could discriminate between the three EV populations. These data contribute to EV-identified miRNA database, especially keratinocyte-derived EV miRNA content.
2019-05-20 | GSE106453 | GEO
Project description:Asthma is a chronic lung disease with various clinical phenotypes, complicating its diagnosis and treatment. The micro-RNA (miRNA) profile of plasma-derived extracellular vesicles (EVs) may serve as potential circulating biomarkers for differentiating asthma phenotypes/endotypes. This study aims to characterize and compare the miRNA profiles in plasma-derived EVs across healthy controls (HC), non-severe asthmatics (NS), and severe asthmatics (SA). EVs were isolated from plasma samples of HC, NS, and SA, followed by physiochemical characterization and RNA isolation. Small RNA sequencing was performed, and differentially expressed (DE) miRNAs were identified through DESeq2 analysis. DE miRNAs and their predicted mRNA targets were identified using Ingenuity Pathway Analysis (IPA), and pathway enrichment was conducted using STRING DB and Enrichr. EVs from all groups were predominantly ~150-200 nm in size, with significantly higher EV counts in SA compared to HC and NS. miRNA expression analysis revealed unique and shared DE miRNAs across the three comparisons (HC vs. NS; HC vs. SA; NS vs. SA). A total of 16 unique DE miRNAs among these comparisons, between which in the NS vs. SA comparison, miR-515-3p positively correlates with lung function, and exacerbation and miR-133a-3p and miR-9-5p with ACT score. Target and pathway analyses from the NS vs. SA comparison indicated the enrichment of key pathways, including IL-4/IL-13, Th1, Th2, and Th17 cell differentiation, MAPK, PI3K-Akt, and receptor tyrosine kinase signaling. This study identified distinct miRNAs in plasma-derived EVs from NS vs. SA which could serve as potential circulating biomarkers for differentiating asthma severity.
2025-09-23 | GSE280322 | GEO