Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

64 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transforming growth factor β (TGFβ) and BMP7 regulate glioblastoma stem cells differentiation status

ABSTRACT: Glioblastoma stem cells (GSCs) fate is controlled by environmental cues, among which cytokines play a crucial role. The transforming growth factor β (TGFβ) family signaling pathways controls GSCs. On one hand, TGFβ promotes cell proliferation in GBM, it induces the expression of platelet-derived growth factor-B (PDGFB). Moreover, TGFβ, via its signaling mediators Smad2/3, induces the expression of the cytokine leukemia inhibitory factor (LIF) and Sox4, which in turn enhances the expression of the stem cell transcription factor Sox2; this increases the self-renewal capacity of the GSCs and their stemness characteristics, and enhances the GSC tumor-initiating potential. On the other hand, Bone morphogenic proteins (BMPs) are known to promote GSC differentiation towards the astrocytic phenotype. To further understand which genes are regulated by TGFβ and BMP7 in GSCs we performed a microarray in the Affymetrix HTA2 platform in three different glioblastoma cell line, U2987, and two patient-derived glioblastoma stem cells, U3031MG and U3034MG, in the presence or absence of 5 ng/ml of TGFβ or 30 ng/ml BMP7 for 24 h, three biological replicates per condition.

ORGANISM(S): Homo sapiens

SUBMITTER: Laia Caja Puigsubirà

PROVIDER: E-MTAB-9076 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Identification of novel BMP target genes in glioblastoma

Project description:It has been previously described that in glioblastoma (GBM), BMPs deplete the tumorigenic potential of glioblastoma stem cells (GSCs), promoting their differentiation towards the astrocytic lineage. To gain more insight on how BMPs regulate differentiation in GSCs, we are interested in identifying new BMP target genes in GBM cells. To this end, the patient derived glioblastoma cell lines U3031MG and U3034MG were stimulated or not with 30ng/ml BMP7 for 2 and 24 h, total RNA was isolated from three biological replicates per condition, and a microarray screen with the Affymetrix U133plus2 platform was performed.

2021-05-01 | E-MTAB-9811 | biostudies-arrayexpress

Transcriptomic analysis by AmpliSeq Ion Torrent to study the involvement of CXXC5 in the regulation of TGFβ/BMP target genes in glioblastoma

Project description:The aim of this work was to elucidate the role of the transcription factor CXXC5 in glioblastoma and study its involvement in the regulation of TGFβ and BMP target genes in this context. To this end we used the patient derived glioblastoma stem cells U3034MG that were either transfected with siRNA targeting CXXC5 or with a non-targeting pool (as control) followed by stimulation with either 5ng/ml TGFβ or 30ng/ml BMP7 for 24 h. Then we analysed how silencing CXXC5 affects the expression of TGFβ and/or BMP7 target genes using Ion torrent AmpliseqTM.

2021-05-01 | E-MTAB-9813 | biostudies-arrayexpress

Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe

Project description:Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors.

2021-09-25 | GSE135306 | GEO

Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in Glioblastoma stem-like cells

Project description:To identify new therapeutic targets for Glioblastoma (GBM), we performed genome-wide CRISPR-Cas9 "knockout" (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem/progenitors (NSCs), non-neoplastic stem cell controls, for genes required for their in vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of molecular networks commonly altered in GBM and GSCs (e.g., oncogenic drivers). In vitro and in vivo validation of GSC-specific targets revealed several strong hits, including the wee1-like kinase, PKMYT1/Myt1. Mechanistic studies demonstrated that PKMYT1 acts redundantly with WEE1 to inhibit Cyclin B-CDK1 activity via CDK1-Tyr15 phosphorylation and to promote timely completion of mitosis in NSCs. However, in GSCs, this redundancy is lost, likely as a result of oncogenic signaling, causing GBM-specific lethality. A whole-genome CRISPR-Cas9 knockout screens targeting over 18,000 genes using the all-in-one LV-sgRNA:Cas9 platform system were performed using a âshot gunâ approach by transducing 2 GBM patient-derived isolates and 2 human neural stem cell isolates with the pool library (2 biological replicates), and cultures were outgrown for ~3 weeks. The end time point of each screen was compared to day 0 in order to determine which sgRNAs were overrepresented or underrepresented in the population.

2016-02-15 | E-GEOD-70038 | biostudies-arrayexpress

ZNF117 target ChIP-seq

Project description:Glioblastoma (GBM) is a deadly disease without effective treatment. Because glioblastoma stem cells (GSCs) contribute to tumor resistance and recurrence, improved treatment of GBM can be achieved by eliminating GSCs through inducing their differentiation. Prior efforts have been focused on studying GSC differentiation towards the astroglial lineage.

2022-02-08 | GSE196067 | 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

Morphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections

Project description:Glioblastoma is a major unmet clinical need characterized by striking inter- and intra-tumoral heterogeneity and a population of glioblastoma stem cells (GSCs), conferring aggressiveness and therapy resistance. GSCs communicate through a network of tumor-tumor connections (TTCs), including nanotubes and microtubes, promoting tumor progression. However, very little is known about the mechanisms underlying TTC formation and overall GSC morphology. As GSCs closely resemble neural progenitor cells during neurodevelopment, we hypothesised that GSCs’ morphological features affect tumour progression. We identified GSC morphology as a new layer of tumoral heterogeneity with important consequences on GSC proliferation. Strikingly, we showed that the neurodevelopmental morphoregulator ADD3, is sufficient and necessary for maintaining proper GSC morphology, TTC abundance and cell cycle progression as well as required for cell survival. Remarkably, both the effects on cell morphology and proliferation depend on the stability of actin cytoskeleton. Hence, cell morphology and its regulators play a key role in tumor progression by mediating cell-cell communication. We thus propose that GSC morphological heterogeneity holds the potential to identify new therapeutic targets and diagnostic markers.

2024-11-12 | GSE280761 | GEO

Microarray analysis of differentiation of human glioblastoma stem cells

Project description:Glioblastoma multiforme is one of the most devastating cancers and presents unique challenges to therapy due to its aggressive behaviour. Cancer stem cells have been described to be the only cell population with tumorogenic capacity in glioblastoma. Therefore, effective therapeutic strategies targeting these cells may be beneficial. We have established different cultures of glioblastoma stem cells (GSCs) derived from surgical specimens and found that, after induction of differentiation, NFκB was activated, which allows intermediate tumor precursor cells to remain cycling. We also showed that blockade of NFκB signaling in differentiating GSCs by different genetic strategies or treatment with small molecule inhibitors, promoted replication arrest, progression to a mature phenotype, mainly neuronal cells, and senescence. This effect was partly mediated by downregulation of the NFκB target gene cyclin D1. Furthermore, intravenous treatment of immunodeficient mice bearing human GSC-derived tumors with a novel small-molecule inhibitor of the NFκB pathway induced senescence of tumor cells but no ultraestructural alterations of the brain parenchymal cells were detected. These findings reveal that activation of NFκB may keep differentiating GSCs from acquiring a mature postmitotic phenotype, thus allowing cell proliferation, and support the rationale for therapeutic strategies aimed at promoting premature senescence in GSCs undergoing differentiation. Gene expression in differentiated cells relative to stem cells in three different glioblastoma cultures

2011-03-01 | E-GEOD-20736 | biostudies-arrayexpress

Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma

Project description:The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which drive tumor growth and treatment resistance.To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown reduced SOX2 transcriptional activity, self-renewal capacity, and in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance.

2021-11-04 | PXD028933 | Pride

Expression profiles of glioblastoma stem cells (GSC) treated with BMP7

Project description:Comparison of untreated and BMP7 treated GSC We used microarrays to identify gene profiles of GSC modulated by BMP7 treatment

2015-10-01 | GSE68030 | GEO