Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Patch-seq of human patient-derived diffuse midline glioma xenografts

ABSTRACT: Patch-seq of human patient-derived diffuse midline glioma xenografts

PROVIDER: PRJNA921869 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Patch-seq of human patient-derived diffuse midline glioma xenografts

Project description:Treatment-resistance of lethal high-grade brain tumors including H3K27M diffuse midline gliomas is thought to arise in part from transcriptional and electrophysiological heterogeneity. These phenotypes are readily studied in isolation using single-cell RNA-seq and whole-cell patch clamping, respectively, but their simultaneous capture is now possible by aspirating a cell's contents into a patch pipet after electrophysiology recordings using a method called 'patch-seq'. Here, we adapt this method to characterize the gene expression programs and functional responses of patient-derived glioma xenografts to neuronal firing at single-cell resolution.

2023-03-01 | GSE222398 | GEO

Gene expression profile at single cell level of Anaplastic ependymoma (EPN) and H3K27M-mutant diffuse midline glioma (BG)

Project description:Anaplastic ependymoma and H3K27M-mutant diffuse midline glioma were analyzed and compared by scRNA-seq.

2024-02-28 | GSE245674 | GEO

Cooperativity between H3-K27M and PDGFRA poses multiple therapeutic vulnerabilities in human iPSC-derived diffuse midline glioma avatars (CUT&RUN)

Project description:PDGFRA and H3.3 mutations cooperate in an iPSC-based model of diffuse midline glioma to alter tumor biology.

2023-06-14 | GSE225490 | GEO

DNA Methylation Potential Energy Landscape Analysis of Diffuse Midline Glioma/Diffuse intrinsic pontine glioma (DMG/DIPG RNA-Seq)

Project description:DNA Methylation Potential Energy Landscape Analysis of Diffuse Midline Glioma/Diffuse intrinsic pontine glioma (DMG/DIPG RNA-Seq)

| PRJNA931330 | ENA

Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas

Project description:The blood-brain barrier (BBB) plays important roles in brain tumor pathogenesis and treatment response, yet our understanding of its function and heterogeneity within or across brain tumor types remains poorly characterized. Here we analyze the neurovascular unit (NVU) of pediatric high-grade glioma (pHGG) and diffuse midline glioma (DMG) using patient derived xenografts and natively forming glioma mouse models. We show tumor-associated vascular differences between these glioma subtypes, and parallels between PDX and mouse model systems, with DMG models maintaining a more normal vascular architecture, BBB function and endothelial transcriptional program relative to pHGG models. Unlike prior work in angiogenic brain tumors, we find that expression of secreted Wnt antagonists do not alter the tumor-associated vascular phenotype in DMG tumor models. Together, these findings highlight vascular heterogeneity between pHGG and DMG and differences in their response to alterations in developmental BBB signals that may participate in driving these pathological differences.

2021-09-01 | GSE179372 | GEO

Venetoclax cooperates with ionizing radiation to attenuate Diffuse Midline Glioma tumor growth

Project description:Venetoclax cooperates with ionizing radiation to attenuate Diffuse Midline Glioma tumor growth

| PRJNA817612 | ENA

Development of an Anti-CD99 Antibody Enables Targeting of Diffuse Midline Glioma

Project description:Development of an Anti-CD99 Antibody Enables Targeting of Diffuse Midline Glioma

| PRJNA1235273 | ENA

Specific cPRC1 complexes are co-opted to mediate oncogenic gene repression in diffuse midline glioma

Project description:Summary Diffuse midline glioma (DMG) is a fatal childhood brain tumour characterised primarily by mutant histone H3 (H3K27M). H3K27M causes a global reduction in Polycomb Repressive Complex 2 (PRC2)-mediated H3K27me3 by inhibiting PRC2 enzymatic activity. Paradoxically, PRC2 is essential in DMG tumour cells where residual complex activity is required for oncogenic gene repression, although the molecular mechanisms acting downstream of PRC2 in this context are poorly understood. Here, we’ve discovered this oncogenic gene repression is mediated by specific canonical PRC1 (cPRC1) formations. By combining CRISPR screening, biochemical and chromatin mapping approaches with functional perturbations we show that cPRC1 complexes containing CBX4 and PCGF4 drive oncogenic gene repression downstream of H3K27me3 in DMG cells. Remarkably, the altered H3K27me3 modification landscape characteristic of these tumours rewires the distribution of cPRC1 complexes on chromatin. CBX4 and PCGF4 containing cPRC1 accumulate at sites of H3K27me3 while other cPRC1 formations are displaced. Despite accounting for <5% of cPRC1 complexes in DMG, CBX4/PCGF4-containing complexes predominate as gene repressors. Our findings link the altered distribution of H3K27me3 with imbalanced cPRC1 function, promoting oncogenic gene repression in DMG cells, revealing new disease mechanisms and highlighting potential therapeutic opportunities in this incurable childhood brain tumour.

2025-06-24 | PXD047451 | Pride

Specific cPRC1 complexes are co-opted to mediate oncogenic gene repression in diffuse midline glioma

Project description:Diffuse midline glioma (DMG) is a fatal childhood brain tumour characterised primarily by mutant histone H3 (H3K27M). H3K27M causes a global reduction in Polycomb Repressive Complex 2 (PRC2)-mediated H3K27me3 by inhibiting PRC2 enzymatic activity. Paradoxically, PRC2 is essential in DMG tumour cells where residual complex activity is required for oncogenic gene repression, although the molecular mechanisms acting downstream of PRC2 in this context are poorly understood. Here, we’ve discovered this oncogenic gene repression is mediated by specific canonical PRC1 (cPRC1) formations. By combining CRISPR screening, biochemical and chromatin mapping approaches with functional perturbations we show that cPRC1 complexes containing CBX4 and PCGF4 drive oncogenic gene repression downstream of H3K27me3 in DMG cells. Remarkably, the altered H3K27me3 modification landscape characteristic of these tumours rewires the distribution of cPRC1 complexes on chromatin. CBX4 and PCGF4 containing cPRC1 accumulate at sites of H3K27me3 while other cPRC1 formations are displaced. Despite accounting for <5% of cPRC1 complexes in DMG, CBX4/PCGF4-containing complexes predominate as gene repressors. Our findings link the altered distribution of H3K27me3 with imbalanced cPRC1 function, promoting oncogenic gene repression in DMG cells, revealing new disease mechanisms and highlighting potential therapeutic opportunities in this incurable childhood brain tumour.

2025-06-24 | PXD058532 | Pride

Therapeutic opportunities for diffuse midline glioma identified from high-throughput combination drug screening

Project description:Therapeutic opportunities for diffuse midline glioma identified from high-throughput combination drug screening

| PRJNA508087 | ENA