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

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

PROVIDER: PRJNA1247788 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33016119_1.fastq.gz	Fastqsanger.gz
	SRR33016119_2.fastq.gz	Fastqsanger.gz
	SRR33016120_1.fastq.gz	Fastqsanger.gz
	SRR33016120_2.fastq.gz	Fastqsanger.gz
	SRR33016121_1.fastq.gz	Fastqsanger.gz

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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.

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Project description:Basal breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells that undergo basal-like plasticity through poorly understood mechanisms. Using genetic mouse models and ex vivo primary organoid cultures, we show that conditional co-deletion of the LATS1 and LATS2 kinases, key effectors of Hippo pathway signaling, in mature mammary luminal epithelial cells promotes the development of basal-like carcinomas that metastasize over time. Genetic co-deletion experiments revealed that phenotypes resulting from the loss of LATS1/2 activity are dependent on the transcriptional regulators YAP/TAZ. Notably, transcriptional analyses of LATS1/2-deleted mammary epithelial cells revealed a gene expression program that associates with human basal breast cancers. Our study demonstrates in vivo roles for the LATS1/2 kinases in mammary epithelial homeostasis and luminal-basal fate control and implicates signaling networks induced upon the loss of LATS1/2 activity in the development of basal breast cancers.

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

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