Leukemia-Derived Small Extracellular Vesicles
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Linjia Jiang
PROVIDER: PXD066914 | iProX | Mon Aug 04 00:00:00 BST 2025
REPOSITORIES: iProX
Similar Datasets
Project description:To characterize the mechanism by which AML derived extracellular vesicles(EV) impaired the vascular architecture and function, EV or PBS injected flk:GFP zebrafish larvae were used for sorting endothelial cells and performing RNA-Seq. Vascular niches sustain hematopoietic stem and progenitor cells (HSPC) and are drastically remodeled in myeloid leukemia to support pathological progression. By utilizing the leukemia-xenografted zebrafish model, we identified that myeloid leukemia secreted extracellular vesicles (EVs) to impair HSPC proliferation, survival and differentiation towards lymphoid/erythroid lineages. The leukemia EVs delivered arginase-1 into venous vasculature to deplete L-arginine and cause NOS uncoupling, which catalyzes production of ROS instead of NO. The oxidative stress caused endothelial cell loss, vascular constriction and failure of secreting niche factors and supporting hematopoiesis. Our findings indicate that myeloid leukemia impaired the vascular function of supporting hematopoiesis by delivering arginase in EVs and arginase inhibition has the potential to improve normal hematopoiesis in myeloid leukemia.
2023-09-01 | GSE229261 | GEO
Project description:Under physiological conditions, extracellular vesicles (EVs) are present simultaneously in the extracellular compartment together with cytokines. Thus, we hypothesized that EVs in combination with cytokines induce different responses of monocyte cells compared to EVs or cytokines alone. Human monocyte U937 cells were incubated with EV-containing or EV-free CCRF human T-cell supernatant, with or without the addition of TNF. U937 cells cultured in EV-free supernatant, supernatant containing CCRF t-cell derived EVs, TNF or both. Each treatment option was measured in 3 replicates.
2013-06-19 | E-GEOD-47897 | biostudies-arrayexpress
Project description:Inflammation in the bone marrow (BM) microenvironment is a constitutive component of acute myeloid leukemia (AML) pathogenesis. Studies have demonstrated that leukemic blasts propagate acute inflammation in the AML niche. Our recent studies in a congenic AML model suggest residual healthy hematopoietic stem and progenitor cells (HSPCs) participate in the inflammatory crosstalk. However, the underlying mechanism that drives the inflammatory conversion of HSPCs remains unclear. Here, we ask whether AML-derived extracellular vesicles (EV-AML) can convert HSPCs into an inflammatory active state in vivo. Using EV-AML purified from inducible (i)MLL-AF9 AML blasts (AF9-EV-AML), we challenged healthy C57BL/6J mice with serial injections of AF9-EVAML and analyzed HSPCs transcriptome. We show that HSPC transcriptome corroborates the enrichment of inflammatory and innate immune responses in EVAML-challenged BM HSPCs compared to controls. Our findings suggest that AML converts HSPCs into an inflammatory hub via EVAML in the AML niche.
2024-04-24 | GSE239307 | GEO
Project description:Acute myeloid leukemia (AML) is an aggressive and heterogeneous clonal disorder of hematopoietic stem/progenitor cells (HSPCs). It is not well known how leukemia cells alter hematopoiesis promoting tumor growth and leukemic niche formation. In this study, we investigated how AML deregulates the hematopoietic process of HSPCs through the release of extracellular vesicles (EVs). First, we found that AML cells released a heterogeneous population of EVs (AML-EVs) containing microRNAs involved in AML pathogenesis. Notably AML-EVs were able to influence the fate of HSPCs modifying their transcriptome. In fact, a gene expression profile of AML-EV-treated HSPCs identified approximately 923 down and 630 up-regulated genes involved in hematopoiesis/differentiation, inflammatory cytokine production and cell movement. Indeed, most of the downregulated genes are targeted by AML-EV-derived miRNAs. Furthermore, we demonstrated that AML-EVs were able to affect HSPCs phenotype, modifying several biological functions, such as inhibiting cell differentiation and clonogenicity, activating inflammatory cytokine production and compromising cell movement. Indeed, a redistribution of HSPC populations was observed in AML-EV treated cells with a significant increase in the frequency of common myeloid progenitors and a reduction in granulocyte-macrophage progenitors and megakaryocyte-erythroid progenitors. This effect was accompanied by a reduction in HSPC colony formation. AML-EV treatment of HSPCs increased the levels of CCL3, IL1B and CSF2 cytokines, involved in the inflammatory process and in cell movement, and decreased CXCR4 expression associated with a reduction of SDF-1 mediated-migration. In conclusion, this study demonstrates the existence of a powerful communication between AML cells and HSPCs, mediated by EVs, which suppresses normal hematopoiesis and potentially contributes to create a leukemic niche favorable to neoplastic development.
2022-03-11 | GSE189492 | GEO
Project description:Under physiological conditions, extracellular vesicles (EVs) are present simultaneously in the extracellular compartment together with cytokines. Thus, we hypothesized that EVs in combination with cytokines induce different responses of monocyte cells compared to EVs or cytokines alone. Human monocyte U937 cells were incubated with EV-containing or EV-free CCRF human T-cell supernatant, with or without the addition of TNF.
2013-06-19 | GSE47897 | GEO
Project description:Overexpression of miR-181a in AML blasts: DNA Microarray was performed to compare overall gene expression profiles of KG-1 Anti-miR-CT and U937 Anti-miR-CT cells compared respectively to KG-1 Anti-miR-181a and U937 Anti-miR-181a.
2014-12-30 | E-MTAB-2837 | biostudies-arrayexpress
Project description:The fetal brain is thought to be dependent upon the placenta for factors that play a specific role in its early development. The tight linkage between the two organs has given rise to the term, the placenta-brain axis. The mouse placenta produces a unique signature pattern of miRNAs target transcripts associated with early fetal brain development, including ones regulating neurogenesis. We hypothesize that placenta-derived extracellular vesicles (EV) transport their molecular cargo, including small RNA, from the placenta to the brain, whereupon their contents can induce pleiotropic effects. We isolated EV from human trophoblast (TB) differentiated in vitro and the parental induced pluripotent stem cells (iPSC) from which the TB was derived, and small RNAseq was done to characterize small RNA profiles within these EV. Human neural progenitor cells (NPC) generated from the same iPSC were exposed to EV derived from TB or iPSC or only treated with control media. Results indicate EV derived from human TB cells contain unique profiles of miRNA and long non-coding RNA (lncRNA) relative to EV isolated from parental iPS cells. Human TB-derived EV readily internalized by human NPC. EV from TB cells induce transcripts in NPC associated with forebrain formation and neurogenesis, suggesting that such EV might program early fetal brain development. Results shed light on the inner workings of the placenta-brain axis. Understanding how contents of TB-derived EV, namely small RNA, affect NPC might yield new insights and potential treatment strategies for neurobehavioral disorders that originate in utero, such as autism spectrum disorders (ASD). The fetal brain is thought to be dependent upon the placenta for factors that play a specific role in its early development. The tight linkage between the two organs has given rise to the term, the placenta-brain axis. The mouse placenta produces a unique signature pattern of miRNAs target transcripts associated with early fetal brain development, including ones regulating neurogenesis. We hypothesize that placenta-derived extracellular vesicles (EV) transport their molecular cargo, including small RNA, from the placenta to the brain, whereupon their contents can induce pleiotropic effects. We isolated EV from human trophoblast (TB) differentiated in vitro and the parental induced pluripotent stem cells (iPSC) from which the TB was derived, and small RNAseq was done to characterize small RNA profiles within these EV. Human neural progenitor cells (NPC) generated from the same iPSC were exposed to EV derived from TB or iPSC or only treated with control media. Results indicate EV derived from human TB cells contain unique profiles of miRNA and long non-coding RNA (lncRNA) relative to EV isolated from parental iPS cells. Human TB-derived EV readily internalized by human NPC. EV from TB cells induce transcripts in NPC associated with forebrain formation and neurogenesis, suggesting that such EV might program early fetal brain development. Results shed light on the inner workings of the placenta-brain axis. Understanding how contents of TB-derived EV, namely small RNA, affect NPC might yield new insights and potential treatment strategies for neurobehavioral disorders that originate in utero, such as autism spectrum disorders (ASD).
2024-11-30 | GSE271631 | GEO
Project description:The expression level of microRNAs in FLT3-ITD+ AML is unknown. Using empty vector (EV) lentiviral CRISPR-Cas9 infected FLT3-ITD+ AML cell lines (MV4-11 cells), we performed next generation RNA sequencing on small RNAs to determine microRNA expression level in these cells. We found a variety of evolutionarily conserved and non-conserved microRNAs expressed in our cells of interest. Small RNAseq on EV lentiviral CRISPR-Cas9 infected MV4-11 cell lines was performed on triplicate cultures.
2016-07-01 | E-GEOD-71543 | biostudies-arrayexpress
Project description:We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies.M-BM- In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk.M-BM- In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. M-BM- Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model.M-BM- Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML. R940406 (R406, the active metabolite of fostamatinib) was supplied by Rigel Pharmaceuticals, Inc., South San Francisco, CA, and AstraZeneca Pharmaceuticals, Wilmington, DE, USA. R406 was resuspended in dimethyl sulfoxide (DMSO) (Sigma-Aldrich) and stored at M-bM-^HM-^R80M-BM-0C. . HL-60, U937 and KG-1 cell lines were purchased from the American Type Culture Collection. MOLM-14 cell lines were provided by Dr. Scott Amstrong (Dana-Farber Cancer Institute, Boston MA, USA.) All cell lines were maintained in RPMI 1640 (Cellgro) supplemented with 1% penicillin-streptomycin and 10% fetal bovine serum (FBS, Sigma-Aldrich) at 37 M-BM-0C with 5% CO2. MOLM-14, U937, HL-60 and KG-1 cells were grown in 4mM R406 for 24 hours
2013-04-24 | E-GEOD-46302 | biostudies-arrayexpress
Project description:PURPOSE: The molecular composition of extracellular vesicles (EV) is regulated by cellular activation and differentiation stimuli, thereby affecting their signaling function to target cells. While activation-associated changes in EV-derived microRNAs (miRNA) have been intensively studied, it is unknown whether cell stimulation affects other classes of small non-coding RNA in EV. METHODS: RNA isolated from primary immune cells that were made tolerogenic with VitD3, activated by LPS, or left untreated (control), and RNA isolated from EV purified from the supernatant of these dendritic cells were analyzed by RNA seq (n = 3 biological replicates) RESULTS: Prominent changes were found in the miRNA, snoRNA and Y-RNA content of EV from differentially stimulated dendritic cells, whereas tRNA and snRNA levels were much less affected. Comparing changes in EV-RNA with changes in the corresponding cells, we found that EV-RNA levels only partly reflected changes in cellular RNA. CONCLUSIONS: Our results implicate that the EV-transcriptome not necessarily predicts RNA levels in EV-producing cells. The acquired knowledge can guide discovery and understanding of non-coding RNA types beyond miRNAs as functional entities in EV and as EV-RNA-based biomarkers.
2018-10-19 | GSE105151 | GEO