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Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells (DNA methylation)

ABSTRACT: Glioblastoma multiforme (GBM) is characterized by the close relationship of glioma stem cells (GSC) with aberrant vascularization. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To elucidate gene regulatory mechanisms of neovascularization both in vitro and in vivo, we performed RNA-seq and DNA methylation profiling of the response of human brain endothelial cells to GSC-EVs as well as histoepigenetic analysis of GBM molecular profiles in the TCGA collection. The gene regulatory responses showed a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Remarkably, EVs and normal vascular growth factors stimulated highly distinct gene regulatory responses, both converging on angiogenesis, providing exciting new insight into targetable angiogenic signaling in GBM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137830 | GEO | 2019/12/20

REPOSITORIES: GEO

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Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells (longRNA-seq)

Project description:Glioblastoma multiforme (GBM) is characterized by the close relationship of glioma stem cells (GSC) with aberrant vascularization. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To elucidate gene regulatory mechanisms of neovascularization both in vitro and in vivo, we performed RNA-seq and DNA methylation profiling of the response of human brain endothelial cells to GSC-EVs as well as histoepigenetic analysis of GBM molecular profiles in the TCGA collection. The gene regulatory responses showed a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Remarkably, EVs and normal vascular growth factors stimulated highly distinct gene regulatory responses, both converging on angiogenesis, providing exciting new insight into targetable angiogenic signaling in GBM.

2019-12-20 | GSE138113 | GEO

Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells (miRNA-seq)

2019-12-20 | GSE138114 | GEO

Expression data in TDEC obtained from irradiated GBM stem cell

Project description:Glioblastomas (GBM) are brain tumors which display a bad prognosis despite conventional treatment associating surgical resection and subsequent radio-chemotherapy. These tumors are defined by an abundant and abnormal vascularization as well as by an important cellular heterogeneity. GBM notably contain a subpopulation of GBM stem-like cells (GSC) which contribute to tumor aggressiveness, resistance, and recurrence. Moreover, GSC directly take part in the formation of new vessels via their transdifferentiation into tumor derived endothelial cells (TDEC). Considering the importance of the vascularization in the GBM, we postulate that radiation could enhance the transdifferentiation of GSC into TDEC. Here, we show that ionizing radiation potentiates endothelial features of TDEC obtained from 3 patient-derived primocultures of GSC. Indeed, TDEC obtained from irradiated GSC (TDEC IR+) migrate more towards VEGF, form more pseudotubes in Matrigel in vitro and develop more functional blood vessel in Matrigel plugs implanted in Nude mice than TDEC obtained from non-irradiated GSC. Transcriptomic analysis allows us to highlight an overexpression of Tie2 in TDEC IR+ which is associated with the activation of AKT signaling pathway. All radiation-induced effects on TDEC IR+ were abolished by using a Tie2 kinase inhibitor, confirming the role of Tie2 signaling pathway in this process. Finally, the number of Tie2+ vessels is increased in recurrent GBM compared with matched untreated tumors. In conclusion, we show that irradiation potentiates proangiogenic features of TDEC throught Tie2/AKT signaling pathway. New therapeutic stategies associating standard teatment and an inhibitor of Tie2 signaling pathway should be considered for forthcoming trials.

2019-10-02 | GSE138236 | GEO

Gene expression profiling of core glioma stem cells: a novel glioblastoma cell population with diminished antigen presentation

Project description:Using induced pluripotent stem cell (iPSC) technology, we reprogrammed GBM derived cells (GBM-DCs) into embryonic-like cells termed as induced core-GSCs (ic-GSCs). The aim of this experiment was to characterize the transcriptomic profile of ic-GSCs using RNA-seq. For this experiment, we selected three biological replicates of GBM-DCs (GBM-DC1, GBM-DC2 and GBM-DC3) and three independent clonal lines of ic-GSCs (ic-GSC#1, ic-GSC#3 and ic-GSC#7).

2022-05-11 | E-MTAB-10977 | biostudies-arrayexpress

DNA methylation profiling of core glioma stem cells: a novel glioblastoma cell population with diminished antigen presentation

Project description:Using induced pluripotent stem cell (iPSC) technology, we reprogrammed GBM derived cells (GBM-DCs) into embryonic-like cells termed as induced core-GSCs (ic-GSCs). The aim of this experiment was to characterize the DNA methylation profile of ic-GSCs using the Infinium MethylationEPIC array BeadChip (850K, Illumina). For this experiment, we selected three biological replicates of GBM-DCs (GBM-DC1, GBM-DC2 and GBM-DC3) and three independent clonal lines of ic-GSCs (ic-GSC#1, ic-GSC#3 and ic-GSC#7).

2022-05-11 | E-MTAB-10978 | biostudies-arrayexpress

EVs MSC miRNA-seq

Project description:The goal of this project was to analyze the EVs cargoes. EVs were isolated from dental pulp mesenchymal stem cells.

2021-09-22 | GSE179940 | GEO

Gene expression in glioblastoma (GBM) tissues, glioblastoma stem-like cell (GSC) cultures and neural foetal cell line (NFC)

Project description:This microarray contains expression data for two GBM tissue samples, four GSC cultures grown as spheres and one NFC culture grown as spheres Total RNA was isolated from GSC cultures and GBM tissues

2015-11-26 | E-GEOD-60705 | biostudies-arrayexpress

Methylation profiling of Glioma Stem Cell lines vs GBM FFPE tissue biopsies and foetal Neural Stem Cell lines

Project description:The DNA methylation profiles of Glioma Stem Cell (GSC) lines were investigated in order to find the stem cell signature associated to glioblastoma (GBM). This goal was achieved through the comparison of GSC methylation data with FFPE-GBM biopsies and human foetal Neural Stem Cell (NSC) lines profiles. GSC lines: 3 (GBM2, G144, G166). FFPE-GBM biopsy pool: FFPE-GBM pool: 1 pool from 5 GBM biopsies. Human foetal NSC lines: 2 (CB660 from forebrain; CB660SP form spinal cord). Methylated DNA from each sample was enriched with the immunoprecipitation method using 5-methylcytosine antibody (Eurogentec). Immunoprecipitated DNA (IP-DNA) and total DNA were labeled and hybridized on Agilent Human CpG Island ChIP-on-Chip Microarray 244K. IP-DNA were labeled with Cy5 while the matching total DNA were labeled with Cy3.

2013-03-08 | E-GEOD-41824 | biostudies-arrayexpress

Endothelial progenitor cells contribute to neovascularization of non-small cell lung cancer via HDAC7 mediated cytoskeleton regulation and angiogenic genes transcription

Project description:To supply tumor tissues with nutrients and oxygen, endothelial progenitor cells (EPCs) are recruited to tumor bed and contribute to tumor neovascularization. HDAC7 is a critical regulator in EPC-mediated neovascularization. To explore the function of HDAC7 in neovascularization induced by EPCs, we use microarrays to profile the genes expression changes in HDAC7 lacking EPCs. HDAC7 silencing upregulated antiangiogenic genes transcription and suppressed proangiogenic genes expression, turning off the angiogenic switch for vessel formation.

2018-12-31 | GSE102178 | GEO

Gene expression data of GBM146 and GBM157 at day0, 7, 30 after serum exposure

Project description:Glioblastoma (GBM) is a lethal brain cancer composed of heterogeneous cellular populations including glioma stem cells (GSCs) and their progeny differentiated non-stem glioma cells (NSGCs). Although accumulating evidence points out the significance of GSCs for tumour initiation and propagation, the roles of NSGCs remain elusive. Here we demonstrate that, when patient-derived GSCs in GBM tumours undergo differentiation with diminished telomerase activity and shortened telomeres, they subsequently become senescent phenotype, thereby secreting angiogenesis-related proteins, including vascular endothelial growth factors. Interestingly, these secreted factors from senescent NSGCs promote proliferation of human umbilical vein endothelial cells and tumorigenic potentials of GSCs in immunocompromised mice. These experimental data are likely clinically-relevant, since immunohistochemistry of both patient tumours of GBM and the patient GSC-derived mouse xenografted tumours detected tumour cells that express a set of markers for the senescence phenotype. Collectively, our data suggest that the inter-cellular signals from senescent NSGCs promote GBM tumour angiogenesis thereby increasing malignant progression of GBM. We monitored gene expression profiling in GSC, differentiated NSGC (GSC at day7 after serum exposure), and senescent NSGC (GSC at day30 after serum exposure) of GBM146 and GBM157.

2015-10-24 | E-GEOD-74304 | biostudies-arrayexpress

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