Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SUV39H1 Maintains Cancer Stem Cells in Glioblastoma [ATAC-seq]

ABSTRACT: Glioblastoma (GBM) is the deadliest brain cancer, driven in part by GBM stem cells (GSCs) that contribute to therapeutic resistance and tumor recurrence. Effective targeting and elimination of GSCs hold promise for preventing GBM recurrence and achieving potential cures. In this study, we explored the role of the epigenetic regulator SUV39H1 in GSC maintenance and GBM progression. We observed that SUV39H1 is upregulated in GBM samples compared to normal brain tissues. Single-cell RNA-seq data indicated that SUV39H1 is preferentially expressed in GSCs relative to non-stem GBM cells, possibly due to super-enhancer-mediated transcriptional activation. Knockdown of SUV39H1 in patient-derived GSCs impaired their proliferation and stemness. RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. Integrated ATAC-seq (assay for transposase-accessible chromatin followed by sequencing) and RNA-seq analyses demonstrated that targeting SUV39H1 altered chromatin accessibility in key genes associated with these pathways. Treatment with chaetocin, a SUV39H1 inhibitor, mimicked the effects of SUV39H1 knockdown in GSCs and sensitized them to the GBM chemotherapy drug temozolomide (TMZ). In vivo studies using an intracranial patient-derived xenograft model showed that targeting SUV39H1 inhibited GSC-driven tumor formation in mice. Our findings identify SUV39H1 as a critical regulator of GSC maintenance and suggest that targeting SUV39H1 could disrupt GSCs and enhance the efficacy of existing chemotherapy, offering a promising strategy for improving GBM treatment outcomes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273013 | GEO | 2024/11/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SUV39H1 Maintains Cancer Stem Cells in Glioblastoma [RNA-seq]

Project description:Glioblastoma (GBM) is the deadliest brain cancer, driven in part by GBM stem cells (GSCs) that contribute to therapeutic resistance and tumor recurrence. Effective targeting and elimination of GSCs hold promise for preventing GBM recurrence and achieving potential cures. In this study, we explored the role of the epigenetic regulator SUV39H1 in GSC maintenance and GBM progression. We observed that SUV39H1 is upregulated in GBM samples compared to normal brain tissues. Single-cell RNA-seq data indicated that SUV39H1 is preferentially expressed in GSCs relative to non-stem GBM cells, possibly due to super-enhancer-mediated transcriptional activation. Knockdown of SUV39H1 in patient-derived GSCs impaired their proliferation and stemness. RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. Integrated ATAC-seq (assay for transposase-accessible chromatin followed by sequencing) and RNA-seq analyses demonstrated that targeting SUV39H1 altered chromatin accessibility in key genes associated with these pathways. Treatment with chaetocin, a SUV39H1 inhibitor, mimicked the effects of SUV39H1 knockdown in GSCs and sensitized them to the GBM chemotherapy drug temozolomide (TMZ). In vivo studies using an intracranial patient-derived xenograft model showed that targeting SUV39H1 inhibited GSC-driven tumor formation in mice. Our findings identify SUV39H1 as a critical regulator of GSC maintenance and suggest that targeting SUV39H1 could disrupt GSCs and enhance the efficacy of existing chemotherapy, offering a promising strategy for improving GBM treatment outcomes.

2024-11-06 | GSE273012 | 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

ZNF117 target ChIP-seq

2022-02-08 | GSE196067 | GEO

Id1 knockdown in primary human glioma stem cells

Project description:Abnormal activation of stemness factors is a crucial signature of cancer stem cells (CSCs), a highly tumorigenic subpopulation in malignant tumors. However, it is unclear whether multi-signaling pathways are activated in CSCs, as like normal stem cells. I would like to report that an inhibitor of differentiation 1 (ID1) activates intracellular multi-signaling involved in proliferation, genesis, and maintenance of glioma stem cells (GSCs) by suppression of Cullin3, an E3 ubiquitin ligase that degrades Cyclin E and components of SHH and WNT signaling. ID1 inhibits BMP-dependent differentiation of GSCs by activation of BMPR2-targeting miR17/20a. ID1HIGH-Cullin3LOW signature correlates with a poor prognosis of GBM patients with a significant association to gene signatures enriched in EGF, WNT, SHH, and BMP signaling. Combinational inhibition of GSC intracellular multi-signaling network increases tumor-bearing mice survival. These results provide insights on molecular and cellular basis of GSC biology, and also suggest necessity of multi-signaling inhibition for GSCs therapy. Two human primary glioma stem cells (GSCs) such as GSC2 and GSC8 were isolated from two individual primary human glioma specimens. The GSCs were directly transfected with pSuper-GFP-ID1-shRNA and pSuper-GFP-Scrambled-shRNA using FuGENE 6 reagent (Roche). The RNA extraction in these cells was used to analyze gene expression.

2013-09-05 | E-GEOD-40614 | biostudies-arrayexpress

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

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

Human glioma stem cell GS5: Control vs. ZNF117 knockout

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. We used microarrays to detail the global programme of gene expression underlying ZNF117 knockout and identified distinct classes of up-regulated genes during this process.

2022-01-31 | GSE187418 | GEO

Targeting of glioma stem-like cells with a parthenolide derivative ACT001 through inhibition of AEBP1/PI3K/AKT signaling

Project description:Glioblastoma (GBM) is the most lethal primary brain tumor in adults with a median survival of around 15 months. A potential treatment strategy involves targeting glioma stem-like cells (GSCs) that are able to initiate, maintain, and repopulate the tumor mass. Here, we identify ACT001, a parthenolide derivative, targeting GSCs through regulation of adipocyte enhancer binding protein 1 (AEBP1) signaling.GSCs exhibit high response to ACT001 in compared with normal human astrocytes. AEBP1 is a putative target of ACT001 by RNA-Seq analysis, which expression associates with prognosis of GBM patients. Knockdown of AEBP1 inhibits GSC proliferation whereas ectopic expression of AEBP1 increases GSC proliferation and xenograft tumor growth. AEBP1 overexpression also attenuates ATC001-inhibited GSC orthotopic xenograft tumor growth. Treatment with ACT001 or PI3K inhibitor or AEBP1 depletion decreases AKT phosphorylation and GSC proliferation. However, constitutive AKT activation rescues ACT001 treatment or AEBP1 knockdown-inhibited cell proliferation. Additionally, ACT001 blocks TGF-β-activated AEBP1/AKT signaling in GSCs. ACT001 exhibits antitumor activity either as a single agent or in combination with SHP099, which provides significant survival benefits for GSC xenograft tumor -bearing animals.

2020-09-11 | GSE157779 | GEO

POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway [GSCs_RNA-seq]

Project description:Glioblastoma (GBM), classified as a grade 4 glioma, is the most prevalent intrinsic malignancy of the central nervous system. Glioblastoma stem cells (GSCs) are small populations of GBM cells with self-renewal and multilineage differentiation capabilities and are considered responsible for the tumorigenesis and development of GBM. GSCs also exhibit radiation resistance, chemoresistance, and angiogenic and invasive properties, which are correlated with poor outcomes in GBM patients. Therefore, targeting GSCs constitutes a promising approach for treating GBM patients. Our findings revealed that POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway.

2024-08-01 | GSE273252 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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