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Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells (scATAC-seq)

ABSTRACT: Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells (scATAC-seq)

PROVIDER: PRJNA943238 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23803106_1.fastq.gz	Fastqsanger.gz
	SRR23803106_2.fastq.gz	Fastqsanger.gz
	SRR23803107_1.fastq.gz	Fastqsanger.gz
	SRR23803107_2.fastq.gz	Fastqsanger.gz
	SRR23803108_1.fastq.gz	Fastqsanger.gz

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Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells (scATAC-seq)

Project description:Understanding prostate response to castration and androgen receptor signaling inhibitors (ARSI) is critical to improving long-term prostate cancer (PCa) patient survival. Here we use a multi-omics approach on 229,794 single cells to create a mouse single-cell reference atlas better suited to interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides chromatin context, which, when coupled with mouse lineage tracing demonstrates that the castration-resistant luminal cells are distinct from the pre-existent urethra-proximal stem/progenitor cells. Molecular pathway analysis and therapeutic studies further implicate JUN/FOS, WNT/b-Catenin, FOXQ1, NFkB, and JAK/STAT pathways as the major drivers of castration-resistant luminal populations with high relevance to human PCa. Importantly, we demonstrate the utility of our datasets, which can be explored through an interactive portal (https://visportal.roswellpark.org/data/tang/), to aid in developing novel combination treatments with ARSI for advanced PCa patients.

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Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells

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Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.

Project description:Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.

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Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells (scRNA-seq)

Project description:Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells (scRNA-seq)

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Expression profile of castration-resistant LY6D+ luminal progenitors during prostate tumourigenesis

Project description:By using luminal lineage tracing model, here we report the regulatory network underlying intrinsically castration-resistant LY6D+ luminal progenitors during prostate tumourigenesis. The luminal cell-specific PTEN deficient mouse model of PCa (K8-CreERT2;PtenFlox/Flox;R26-StopFlox/Flox-EYFP (K8PY) and the control K8-CreERT2;R26-StopFlox/Flox-EYFP (K8Y) mice) are used in this study.

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Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration

Project description:Identification of defined cell populations with stem/progenitor properties is key for our understanding of prostate development and tumorigenesis. Prior studies have provided strong evidence of the existence of prostate luminal progenitors, but their identity and functional properties remains unknown. Using an unbiased novel bigenic mouse model to specifically earmark, prospectively isolate, and functionally characterize the quiescent stem-like cells, we identify a label-retaining cell (LRC) population in the mouse prostate luminal cell layer as candidate luminal progenitors. Through comprehensive molecular and biological characterizations, we show that these luminal LRCs exhibit relative dormancy with significant enrichment in the mouse proximal prostate, display bipotent potential in both in vitro organoid formation and the in vivo prostate regeneration assay, express a stem/progenitor gene signature with resemblance to aggressive prostate cancer. Importantly, these luminal LRCs maintain a lower level of Ar expression, are androgen-independent, and resist castration in vivo. Furthermore, analysis of phenotypic markers by immunefluorescent staining reveals heterogeneity within luminal progenitor cell pool. Collectively, our studies establish luminal LRCs as progenitors that may serve as a cellular origin for castration resistant prostate cancer.

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Expression profile of castration-resistant LY6D+ luminal progenitors during prostate tumourigenesis

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Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.

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

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