Similar Datasets
Project description:Effect of CD97 knockdown or overexpression in patient-derived GBM cultures (PDGCs)
| PRJNA961053 | ENA
Project description:Glioblastoma (GBM) stem cells (GSCs) are largely associated with a poor prognosis of GBM. Although the importance of identifying and validating molecular markers in GBM has been emphasized, single markers covering all GSCs are lacking. Through in vitro antibody screening, in this study, we demonstrated that CD97 identifies GSCs as a novel surface marker. Compared to conventional well-known GSC markers, such as CD133, CD44 and CD15, only CD97 was notably detected in all tested patient-derived GSCs. GBM patients expressing high levels of CD97 experienced worse clinical outcomes, and were predictive of poor overall survival in the public database. CD97 is required for GSC proliferation and self-renewal and was shown to reduce mouse survival with aggressive tumor progression in an orthotopic xenograft model. A comparative transcriptomic analysis revealed that CD97 triggers mTORC2 signaling through Akt (S473) phosphorylation, enhancing the expression of downstream genes, including ARHGAP1, BZW1, and BZW2. Moreover, inhibition of mTORC2 signaling with the pharmacological inhibitor JR-AP2-011 suppressed GSC proliferation, self-renewal, and downstream gene expression. Furthermore, sorting of CD97-enriched cells from patient-derived GSCs revealed that CD97 promotes GSC self-renewal and tumorigenicity via mTORC2/AKT signaling. Thus, our findings suggest that CD97 may be a general GSC enrichment marker in GBM and that the CD97-related pathway might serve as a therapeutic target for GBM.
2024-12-03 | GSE201960 | GEO
Project description:Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their functional role in gliomagenesis and their potential as treatment targets. To identify therapeutically targetable opportunities among aGPCR family members in an unbiased fashion, we analyzed expression levels of all aGPCRs in GBM and non-neoplastic brain tissue. Using bulk and single cell transcriptomic and proteomic data, we show that CD97 (ADGRE5), an aGPCR previously implicated in GBM pathogenesis, is the most promising aGPCR target in GBM, by virtue of its abundance in all GBM tumors and its de novo expression profile in GBM compared to normal brain tissue and neural progenitors. CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cells (PDGC) in vitro and in vivo. Transcriptomic and metabolomic data from PDGCs suggest that CD97 promotes glycolytic metabolism. The oncogenic and metabolic effects of CD97 are mediated by the MAPK pathway. Activation of MAPK signaling depends on phosphorylation of the cytosolic C-terminus of CD97 and recruitment of -arrestin. Using single-cell RNA-sequencing and biochemical assays, we demonstrate that THY1/CD90 is the most likely CD97 ligand in GBM. Lastly, we show that targeting of GBM cells with an anti-CD97 antibody-drug conjugate in vitro selectively kills tumor cells but not human astrocytes or neural stem cells. Our studies identify CD97 as an important regulator of tumor metabolism in GBM, elucidate mechanisms of receptor activation and signaling, and provide strong scientific rationale for developing biologics to target CD97 in GBM.
2023-12-01 | GSE230389 | GEO
Project description:We analyzed the transcriptome differences of wild-type, CD97- and Gα13-deficient (Adgre5-/- and CD11c-cre x Gna13fl/fl) type-2 conventional dendritic cells (cDC2s) in spleen. Three technical repeats of ~10^5 cells per sample from each of one mouse were included. Compared to wild-type cDC2s, CD97- and Gα13-deficient cDC2s differentially expressed many genes, but CD97- and Gα13-deficient cDC2s were almost the same. GSEA showed that Mrtf-a dependent genes were upregulated in CD97- and Gα13-deficient cDC2s, which code for cytoskeleton proteins. These data support that CD97-Gα13 signaling regulates splenic cDC2 motility by the actin cytoskeleton.
2022-03-23 | GSE188828 | GEO
Project description:Despite significant efforts to improve therapies for acute myeloid leukemia (AML), clinical outcomes remain poor. Understanding the mechanisms that regulate the development and maintenance of leukemic stem cells (LSC) is important to reveal new therapeutic opportunities. We have identified CD97, a member of the adhesion class of G-protein coupled receptors (GPCRs), as a frequently upregulated antigen of AML blasts that is a critical regulator of blast function. High levels of CD97 correlate with poor prognosis, and silencing of CD97 reduces disease aggressiveness in vivo. In order to analyze the functional pathways associated with CD97 expression, we generated RNA-sequence data from scrambled shRNA transfected (s-shRNA) and CD97 KD human AML cell line HL60, as well as from MLL-AF9 (MA9) transduced GMPs isolated from CD97-/- and WT mice. These phenotypes are due to CD97’s function to promote proliferation, survival, and the maintenance of the undifferentiated state in leukemic blasts. Collectively, our data credential CD97 as a promising therapeutic target on LSCs in AML.
2019-07-30 | GSE135028 | GEO
Project description:Genome wide DNA methylation profiling of GBM xenografts. The Illumina EPIC 850k Human DNA methylation array used to obtain DNA methylation profiles across approximately 800,000 CpGs in GBM xenograft samples. Samples included xx GBM xenografts.
2019-06-26 | GSE132650 | GEO
Project description:Our adult GBM patient-derived xenograft mouse models keep the genomics characteristics of GBM patient tumors.
2023-07-12 | GSE207886 | GEO
Project description:The recent incorporation of molecular features into the diagnosis of Glioblastoma Multiforme patients has led to an improved categorisation into different tumour subtypes with different prognosis and disease management. In this work, we have exploited the benefits of genome-wide multiomic approaches to identify potential molecular vulnerabilities existing on GBM patients. We used the Illumina MethylationEPIC Beadchip platform to describe the genome-wide 5mC and 5hmC DNA methylation landscape of a total of 9 patient-derived Glioblastoma Multiforme Cell lines obtained from the human glioblastoma cell culture resource (HGCC) and 4 brain samples obtained from non-tumoral controls
2023-06-01 | E-MTAB-12473 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is the most common primary malignant cancer of the central nervous system. Hypoxia, low oxygen, has been linked to GBM infiltration and aggressive tumor progression leading to poor patient outcome. Hypoxia-induced pathways are activated by the stabilization of HIF1-α, which upregulates genes related to reprogramming metabolism, angiogenesis, cell trafficking, and cell survival. However, underlying mechanisms of HIF-1α involvement with GBM cell specific pathways is not fully understood. Here, we show that hypoxia can induce specific genes dependent on GBM subtype. In a in vitro migration assay, we screened eight patient-derived GBM stem cell lines. Two lines, UCA and UNB, were found to induce an increased migration ability in response to hypoxia. By RNA bulk sequencing, we identified key specific genes that were upregulated in each cell line that were not shared between them. Furthermore, we found that this data set correlates to previous single-cell RNA sequencing findings of GBM having differentiated transcriptional subtypes. Our results demonstrate how hypoxia induces a specific response in tumor cells by activating genes for survival and tumor progression. Our study forms the basis for future approaches to characterize top candidate genes and elucidate their role in tumor survival in response to hypoxia. Inhibition of these top candidate genes can be a strategy used to dampen hypoxia pro-tumor properties and may lead to better outcomes for GBM patients.
2024-02-20 | GSE232725 | GEO
Project description:Next Generation Sequencing from control and CD97 knockdown of glioblastoma stem cells
| PRJNA833863 | ENA