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Distinct mesenchymal cell states mediate prostate cancer progression [Spatial Transcriptomics]

ABSTRACT: Distinct mesenchymal cell states mediate prostate cancer progression [Spatial Transcriptomics]

PROVIDER: PRJNA1044082 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26919472.fastq.gz	Fastqsanger.gz
	SRR26919473.fastq.gz	Fastqsanger.gz

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Distinct mesenchymal cell states mediate prostate cancer progression [Spatial Transcriptomics]

Project description:We sought to determine whether molecular alterations in tumor stroma influence prostate cancer progression and metastatic potential. To accomplish this, we compared mesenchymal cells from four genetically engineered mouse models (GEMMs) of prostate cancer representing different stages of the disease to their wild-type (WT) counterparts by single-cell RNA sequencing (scRNA-seq) and, ultimately, to human tumors with comparable genotypes. We identified 8 transcriptionally and functionally distinct stromal populations responsible for both common and GEMM-specific transcriptional programs. These are conserved between mouse models and human prostate cancers with the same genomic drivers. The transcriptional profiles of the stroma of murine models of advanced disease were similar to those of human prostate cancer bone metastases, with periostin expression by stromal cells influencing invasion and neuroendocrine differentiation. These profiles were then used to build a robust gene signature that can predict metastatic progression in localized disease independent of Gleason score. Taken together, this offers new evidence that the stromal microenvironment mediates prostate cancer progression.

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Distinct mesenchymal cell states mediate prostate cancer progression

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Distinct mesenchymal cell states mediate prostate cancer progression (mouse)

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Distinct mesenchymal cell states mediate prostate cancer progression (human)

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Distinct mesenchymal cell states mediate prostate cancer progression.

Project description:Alterations in tumor stroma influence prostate cancer progression and metastatic potential. However, the molecular underpinnings of this stromal-epithelial crosstalk are largely unknown. Here, we compare mesenchymal cells from four genetically engineered mouse models (GEMMs) of prostate cancer representing different stages of the disease to their wild-type (WT) counterparts by single-cell RNA sequencing (scRNA-seq) and, ultimately, to human tumors with comparable genotypes. We identified 8 transcriptionally and functionally distinct stromal populations responsible for common and GEMM-specific transcriptional programs. We show that stromal responses are conserved in mouse models and human prostate cancers with the same genomic alterations. We noted striking similarities between the transcriptional profiles of the stroma of murine models of advanced disease and those of of human prostate cancer bone metastases. These profiles were then used to build a robust gene signature that can predict metastatic progression in prostate cancer patients with localized disease and is also associated with progression-free survival independent of Gleason score. Taken together, this offers new evidence that stromal microenvironment mediates prostate cancer progression, further identifying tissue-based biomarkers and potential therapeutic targets of aggressive and metastatic disease.

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Distinct mesenchymal cell states mediate prostate cancer progression.

Project description:In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species. Notably, stromal signatures in advanced mouse disease reflect those in human bone metastases, highlighting periostin's role in invasion and differentiation. From these insights, we derive a gene signature that predicts metastatic progression in localized disease beyond traditional Gleason scores. Our results illuminate the critical influence of stromal dynamics on PCa progression, suggesting new prognostic tools and therapeutic targets.

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Distinct mesenchymal cell states mediate prostate cancer progression

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

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