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BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [scRNA-seq]

ABSTRACT: BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [scRNA-seq]

PROVIDER: PRJNA877247 | ENA |

REPOSITORIES: ENA

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BAF complex maintains glioma stem cells in pediatric H3K27M-glioma

Project description:BAF complex maintains glioma stem cells in pediatric H3K27M-glioma

| PRJNA877246 | ENA

BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [scRNA-seq]

Project description:Diffuse midline gliomas (DMGs) are uniformly fatal pediatric central nervous system cancers, refractory to standard of care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3.3 and H3.1, K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape, which we interrogated here for epigenetic dependencies using a CRISPR screen in patient-derived H3K27M-glioma neurospheres. We show that H3K27M-glioma cells are dependent on core components of the mammalian SWI/SNF (BAF) chromatin remodeling complex for maintaining glioma stem cells in a cycling, oligodendrocyte precursor cell (OPC)-like state. Genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacological suppression opposes proliferation, promotes differentiation, and improves overall survival of patient-derived xenograft (PDX) models. In summary, we demonstrate that therapeutic inhibition of BAF complex has translational potential for children with H3K27M-gliomas.

2022-09-15 | GSE212782 | GEO

BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [RNA-seq]

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BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [ChIP-seq]

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BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [ATAC-seq]

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BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [ChIP-seq]

Project description:BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [ChIP-seq]

| PRJNA876906 | ENA

BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [RNA-seq]

Project description:BAF complex maintains glioma stem cells in pediatric H3K27M-glioma [RNA-seq]