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

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

PROVIDER: PRJNA876941 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21425172_1.fastq.gz	Fastqsanger.gz
	SRR21425172_2.fastq.gz	Fastqsanger.gz
	SRR21425173_1.fastq.gz	Fastqsanger.gz
	SRR21425173_2.fastq.gz	Fastqsanger.gz
	SRR21425174_1.fastq.gz	Fastqsanger.gz

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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]

2022-09-15 | GSE212718 | GEO

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]

2022-09-15 | GSE212679 | GEO

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

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

| PRJNA876732 | ENA

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 [scRNA-seq]

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

| PRJNA877247 | ENA

BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma.

Project description:Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell-like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas.SignificanceEpigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1-BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma. See related commentary by Beytagh and Weiss, p. 2730. See related article by Mo et al., p. 2906.

| S-EPMC9716260 | biostudies-literature

BAF complex maintains glioma stem cells in pediatric H3K27M-glioma

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-15 | GSE212786 | GEO