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ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scATAC-seq]

ABSTRACT: ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scATAC-seq]

PROVIDER: PRJNA1080280 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28088710_1.fastq.gz	Fastqsanger.gz
	SRR28088710_2.fastq.gz	Fastqsanger.gz
	SRR28088711_1.fastq.gz	Fastqsanger.gz
	SRR28088711_2.fastq.gz	Fastqsanger.gz
	SRR28088712_1.fastq.gz	Fastqsanger.gz

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ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scATAC-seq]

Project description:Performed scATAC-seq in 3 timepoints of an autochthonous mouse model. A proliferative population is characterized by an ERG-specific chromatin state enriched for NFkB, AP-1, STAT and NFAT binding, with implications for TF cooperativity. ERG is enriched in a small stem-like population implicates the chromatin context of these cells as a critical variable for unmasking its oncogenic activity.

2025-04-07 | GSE258962 | GEO

ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scRNA-seq]

Project description:Performed scRNA-seq of an autochthonous mouse model at an early stage of disease initiation. Despite broad expression of ERG in all prostate epithelial cells, proliferation was enriched in a small, stem-like population of cells with mixed-luminal basal identity (intermediate cells).

2025-04-07 | GSE257543 | GEO

ERG-driven gene expression in basal and luminal cells of mouse prostate organoids

Project description:ETS transcription factor ERG is aberrantly activated in ~50% of human prostate cancers. We found that ERG shows a preference of basal over luminal context to drive prostate cancer. However, the molecular basis of the cell context dependency remains elusive. Here we use ERG+/+;Pten-/- (EP) mouse prostate organoids with dual basal/luminal lineage reporters to profile ERG-driven gene expression programs from sorted basal vs luminal cells.

2025-04-12 | GSE294013 | GEO

ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scRNA-seq]

Project description:ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scRNA-seq]

| PRJNA1080200 | ENA

ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity.

Project description:To gain insight into how ERG translocations cause prostate cancer, we performed single cell transcriptional profiling of an autochthonous mouse model at an early stage of disease initiation. Despite broad expression of ERG in all prostate epithelial cells, proliferation was enriched in a small, stem-like population with mixed-luminal basal identity (called intermediate cells). Through a series of lineage tracing and primary prostate tissue transplantation experiments, we find that tumor initiating activity resides in a subpopulation of basal cells that co-express the luminal genes Tmprss2 and Nkx3.1 (called BasalLum) but not in the larger population of classical Krt8+ luminal cells. Upon ERG activation, BasalLum cells give rise to the highly proliferative intermediate state, which subsequently transitions to the larger population of Krt8+ luminal cells characteristic of ERG-positive human cancers. Furthermore, this proliferative population is characterized by an ERG-specific chromatin state enriched for NFkB, AP-1, STAT and NFAT binding, with implications for TF cooperativity. The fact that the proliferative potential of ERG is enriched in a small stem-like population implicates the chromatin context of these cells as a critical variable for unmasking its oncogenic activity.

| S-EPMC10996491 | biostudies-literature

ERG-driven gene expression in basal and luminal cells of mouse prostate organoids

Project description:ERG-driven gene expression in basal and luminal cells of mouse prostate organoids

| PRJNA1247788 | ENA

Erg

Project description:Rattus norvegicus Erg, ETS transcription factor ERG [Source:RGD Symbol;Acc:621108], is differentially expressed in 18 experiment(s);

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ERG

Project description:Monodelphis domestica ERG, ETS transcription factor ERG [Source:NCBI gene;Acc:100019086], is expressed in 2 baseline experiment(s);

| ENSMODG00000020980 | ExpressionAtlas

Erg

Project description:Rattus norvegicus Erg, ETS transcription factor ERG [Source:RGD Symbol;Acc:621108], is expressed in 5 baseline experiment(s);

| ENSRNOG00000001652 | ExpressionAtlas

Epigenome-wide impact of MAT2A sustains the androgen-indifferent state and confers synthetic vulnerability in ERG fusion-positive prostate cancer

Project description:Castration-resistant prostate cancer (CRPC) is a frequently occurring disease with adverse clinical outcomes and limited therapeutic options. Here, we identify a novel role of methionine adenosyltransferase 2a (MAT2A) as a driver of the androgen-indifferent state in ERG fusion-positive CRPC. We show that MAT2A is upregulated in CRPC and cooperates with ERG in promoting cell plasticity, stemness and tumorigenesis. RNA, ATAC and ChIP sequencing coupled with mass spectrometry analysis of histone post-translational modifications show that MAT2A broadly impacts the transcriptional and epigenetic landscape. MAT2A enhances H3K4me2 at multiple genomic sites promoting the expression of pro-tumorigenic non-canonical AR target genes in CRPC models. Genetic and pharmacological inhibition of MAT2A in preclinical models reversed this transcriptional and epigenetic remodeling, promoting luminal differentiation and improving the response to AR and EZH2 inhibitors. This data reveals a previously unrecognized function of MAT2A in epigenetic reprogramming and a synthetic vulnerability to MAT2A inhibitors in ERG fusion-positive CRPC.

2024-06-06 | PXD042895 | Pride

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