Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide expression profiling of CUTTL1 cells upon miR-17-92 cluster overexpression with or without gamma-secretase inhibitor treatment

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive T-cell malignancy characterized by genotypically-defined and phenotypically divergent cell populations, governed by adaptive landscapes. Clonal expansions are associated to genetic and epigenetic events, and modulation of external stimuli that affect the hierarchical structure of subclones and support the dynamics of leukemic subsets. Recently, extracellular vesicles (EVs) such exosomes were also shown to play a role in leukemia. Here, we explored the role of EVs in the realm of Notch-driven T-ALLs and found that T-ALL cells secrete Notch-dependent EVs containing microRNAs (EV-miRs), which control oncogenic pathways acting as autocrine stimuli and promote in vitro the expansion/survival of cell subsets of human T-cell leukemias. Of interest, the highlighted Notch-dependent EV-miRs mostly comprised members of miR-17-92a cluster and paralogues, which rescued in vitro the proliferation of T-ALL cells induced by γ-secretase inhibitors (GSI). Additionally, single-cell RNA sequencing analysis of leukemia cells from primary T-ALL patients revealed cell subsets differently responsive to Notch-dependent EV-miRs. All these findings suggest that restricted EV-miRs may sustain the growth/survival of immunophenotypically defined cell populations, altering the cell heterogeneity and the dynamics of T-cell leukemias in response to conventional therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193482 | GEO | 2022/12/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Osteoblasts secrete miRNA-containing extracellular vesicles that enhance expansion of human umbilical cord blood cells

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

Development of gene expression signatures with lncRNAs for T-cell subsets (CD34+ and CD4+CD8+)

Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. Gene expression was measured in sorted T-cell subsets of 4 healthy donors.

2014-10-27 | E-GEOD-61873 | biostudies-arrayexpress

Differential microRNA profiles of intramuscular and secreted extracellular vesicles in human tissue-engineered muscle

Project description:Exercise affects the expression of microRNAs (miR/s) and muscle-derived extracellular vesicles (EVs). To evaluate sarcoplasmic and secreted miR expression in human skeletal muscle in response to exercise-mimetic contractile activity, we utilized a three-dimensional tissue-engineered model of human skeletal muscle (“myobundles”). Myobundles were subjected to three culture conditions: no electrical stimulation (CTL), chronic low frequency stimulation (CLFS), or intermittent high frequency stimulation (IHFS) for 7 days. RNA was isolated from myobundles and from extracellular vesicles (EVs) secreted by myobundles into culture media; miR abundance was analyzed by miRNA-sequencing. We used edgeR and a within-sample design to evaluate differential miR expression and Pearson correlation to evaluate correlations between myobundle and EV populations within treatments with statistical significance set at p<0.05. Numerous miRs were differentially expressed between myobundles and EVs; 116 miRs were differentially expressed within CTL, 3 within CLFS, and 2 within IHFS. Additionally, 25 miRs were significantly correlated (18 in CTL, 5 in CLFS, 2 in IHFS) between myobundles and EVs. Electrical stimulation resulted in differential expression of 8 miRs in myobundles and only 1 miR in EVs. Several KEGG pathways, known to play a role in regulation of skeletal muscle, were enriched, with differentially overrepresented miRs between myobundle and EV populations identified using miEAA. Together, these results demonstrate that in vitro exercise-mimetic contractile activity of human engineered muscle affects both their expression of miRs and number of secreted EVs. These results also identify novel miRs of interest for future studies of the role of exercise in organ-organ interactions in vivo

2022-09-28 | GSE203157 | GEO

Crosstalk between the effects of extracellular vesicles (Evs) and TNF on U937 human monocyte cell line

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

Proteomic signatures of extracellular vesicles secreted by non-mineralizing and mineralizing human osteoblasts and stimulation of tumor cell growth

Project description:Beyond forming bone, osteoblasts play pivotal roles in various biological processes, including hematopoiesis and bone metastasis. Extracellular vesicles (EVs) have recently been implicated in intercellular communication via transfer of proteins and nucleic acids between cells. Here, we focused on the proteomic characterization of non-mineralizing (NMOBs) and mineralizing (MOBs) human osteoblast (SV-HFOs) EVs and investigated their effect on human prostate cancer (PC3) cells by microscopic, proteomic and gene expression analyses. Proteomic analysis showed that 97% of the proteins were shared among NMOB and MOB EVs, and 30% were novel osteoblast-specific EV proteins. Label-free quantification demonstrated mineralization stage-dependent five-fold enrichment of 59 and 451 EV proteins in NMOBs and MOBs, respectively. Interestingly, bioinformatic analyses of the osteoblast EV proteomes and EV-regulated prostate cancer gene expression profiles showed that they converged on pathways involved in cell survival and growth. This was verified by in vitro proliferation assays where osteoblast EV uptake led to two-fold increase in PC3 cell growth compared to cell-free culture medium-derived vesicle controls. Our findings elucidate the mineralization stage-specific protein content of osteoblast-secreted EVs, show a novel way by which osteoblasts communicate with prostate cancer, and open up innovative avenues for therapeutic intervention. PC3 cells were treated with extracellular vesicles from non-mineralizing and mineralizing SV-HFOs for three different incubation times (4hrs, 24hrs, 48hr)

2014-10-28 | E-GEOD-56172 | biostudies-arrayexpress

proteomic profiling of small extracellular vesicles (EVs), released by chronic myeloid leukemia cells K562

Project description:Chronic and acute myeloid leukemia (CML/AML) evade immune surveillance and induce immunosuppression, largely by upregulating Foxp3+ regulatory T cells (Treg). However, mechanisms that drive Treg in myeloid leukemias are largely unknown. Here, we show that leukemic (CML- and AML-derived) extracellular vesicles (EVs) drive human Treg, by de novo induction of Treg and by upregulating suppressive phenotype and activity of Treg. Rab27a-mediated EVs secretion contributed to Treg expansion, activity, and leukemic engraftment in vivo in a mouse model of CML-like disease. Leukemic EVs downregulated mTOR-S6 and upregulated STAT5 signaling in T cells, to upregulate Foxp3 and Treg activity, as well as evoked significant transcriptomic changes in Treg. By using high resolution 23-color spectral flow cytometry we identified 2 distinct, highly suppressive subsets of Treg expanded by leukemic EVs, characterized by elevated expression of tumor Treg markers CCR8, CCR4, TIGIT, CD39, CD30, TNFR2 and IL21R. Finally, we identified 4 1BBL/TNFSF9 protein in leukemic EVs. Deficiency of 4-1BBL in leukemic cells and EVs resulted in lower expression of CD30, TNFR2 and LAG-3 on Treg and thus weaker effector phenotype. Collectively, our data pinpoint leukemic extracellular vesicles as a significant factor that drives regulatory T cells and immunosuppression in myeloid leukemias. Our results suggest that targeting of Rab27a and EVs secretion may be a viable therapeutic option in myeloid leukemias, whereas detection of 4 1BBL containing EVs could be used as an early biomarker of immunosuppression and leukemia development/relapse

2022-02-16 | PXD027240 | Pride

Extracellular vesicle microRNA profiling in synovial fluids and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients: methodological challenges and identification of putative disease biomarkers

Project description:New early low-invasive biomarkers are demanded for the management of Oligoarticular Juvenile Idiopathic Arthritis (OJIA), the most common chronic inflammatory arthritis in childhood and a leading cause of disability. Extracellular vesicles (EVs) released in the synovial fluid (SF) of inflamed joints have gained increased recognition as mediators of arthritis pathogenesis and as a source of biomarkers. No standardized protocol is available, yet, for the analysis of EV-derived microRNAs (EV-miRs) in human SF specimens, and their potential as biomarkers in OJIA has not been explored. This study proposes an optimized procedure for profiling EV-miRs in SF and represents the first investigation of the miRNome in EV isolated from OJIA patients at disease onset. We present data showing efficient recovery of EVs from SF aspirates and optimal profiling of their miRNA content. We identified a subset of 15 EV-miRs whose expression was deregulated in SF. Analysis of EV-miRs target genes evidenced the enrichemnt of processes related to inflammation, cartilage/bone homeostasis, hypoxia, and hormone metabolism, suggesting their contribution to disease pathogenesis and potential as new putative biomarkers. In addition, we detected altered expression levels of several circulating EV-miRs able to discriminate new-onset OJIA patients from control children. Among them, 16 were consensually overexpressed in both PL and SF from OJIA patients respect to controls, potentially representing a disease-associated molecular “fingerprint” measurable at both the systemic and local levels with high diagnostic potential. These results improve our understanding of OJIA molecular mechanisms and provide an important contribution in the search of new candidate biomarkers for early OJIA diagnosis and the design of novel tailored therapies.

2022-12-30 | GSE191326 | GEO

EV-miRome-wide identification of noncoding RNAs for detecting metastatic colorectal cancer and monitoring the therapeutic response

Project description:Molecular composition of circulating small extracellular vesicles (EVs) does not merely reflect the cells of origin, but also is enriched in specific biomolecules directly associated with the cellular transformation. Given their functional and clinical relevance, small EVs have emerged as a promising target among the liquid biopsy approaches for cancer detection. However, while most of the currently identified EV-miRs are only geared towards one-dimensional disease detection, their application for long-term tracking and treatment response monitoring has been largely elusive. In this study, we established and optimized a rapid, sensitive and robust liquid biopsy sampling method, and further used small RNA sequencing to comprehensively catalogue EV-miRomes in association with the progression and outcome of metastatic colorectal cancer (mCRC). By cross-comparison of EV-miRomes (n = 290) from multi-stage and longitundial cohorts, we uncovered 28 EV-miRs for detecting mCRC, and 131 EV-miRs for long-term monitoring of tumor size progression. Among these candidates, we further pinpointed a 15-EV-miR signature with dual detection and monitoring functions for mCRC. From this panel, EV-miR-320c was uncovered as a strong clinical marker – aside from its diagnostic power, its high expression has also been linked to lower overall survival and a greater likelihood of disease recurrence. Furthermore, target spectrum of this 15-EV-miR signature of mCRC suggested an involvement of small EVs in programming the mesenchymal–epithelial transition (MET) transition for distant localization of the metastasized cells and also in creating a tumor-favoring metastatic niche. Our clinically-oriented delineation of the mCRC-associated circulating EV-miRomes revealed the functional significance of these liquid biopsy markers and further strengthen their translational potential in tumor therapeutic monitoring.

2022-09-14 | GSE188627 | GEO

Low input RNA-seq of endothelial cells sorted from tail of zebrafish larvae

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

Jurkat cell exosomes bound by CD47, CD63 and MHC1 harbor different RNA content

Project description:Extracellular vesicles (EVs) mediate cell-cell communication including the intercellular transfer of RNAs, which alter gene expression in target cells. However, heterogeneity in the size, density, and composition of EVs has limited progress towards defining their physiological functions and utility as disease-specific biomarkers. CD63 and MHC-1 are widely used as markers to purify EVs. CD47 is also present on EVs and alters their effects on target cells, suggesting that specific surface markers define functionally distinct EVs. This hypothesis was addressed by comparing the properties of Jurkat T cell EVs captured using CD47, CD63, and MHC-1 antibodies. These EV subsets have similar sizes but divergent RNA contents.

2018-03-13 | GSE103493 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data