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Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [scRNA-Seq]

ABSTRACT: Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [scRNA-Seq]

PROVIDER: PRJNA692211 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13438502_1.fastq.gz	Fastqsanger.gz
	SRR13438502_2.fastq.gz	Fastqsanger.gz
	SRR13438503_1.fastq.gz	Fastqsanger.gz
	SRR13438503_2.fastq.gz	Fastqsanger.gz

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Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [scRNA-Seq]

Project description:Epidemiological data have linked vitamin D deficiency to the onset of various cancers, including prostate cancer, and although in-vitro studies have demonstrated anti-cancer activities for the vitamin, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically-engineered mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analogue with reported anti-cancer activities, and comprehensively analyzed its effects on various cell types in such lesions. We show that this analogue induces apoptosis in senescent PINs and normalizes extracellular matrix remodeling by stromal fibroblasts in an epithelial VDR-dependent manner. Furthermore, it reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells in an epithelial VDR-independent manner. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal epithelial cells, expressing Krt4 and Tacstd2 (termed luminal-C) with enhanced interferon signature, is lost by such a treatment, anti-apoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of prostatic precancerous lesions and the microenvironment to the vitamin D analogue, and shed light on mechanisms that limit treatment’s efficacy.

2021-08-04 | GSE164856 | GEO

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions

Project description:Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions

| PRJNA692208 | ENA

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [RNA-Seq]

Project description:Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [RNA-Seq]

| PRJNA692210 | ENA

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions [RNA-Seq]

Project description:We treated PTENpe-/- mice, in which PTEN is selectively ablated in prostatic epithelial cells, with a Vitamin D analog. We extracted RNA from the prostate of oil (vehicle) and Vitamin D analog-treated mice.

2021-08-04 | GSE164855 | GEO

Single-cell analyses unravel cell type-specific responses to a vitamin D analogue in prostatic precancerous lesions

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

2021-08-04 | GSE164858 | GEO

Single-cell analyses unravel cell type-specific responses to a vitamin D analog in prostatic precancerous lesions.

Project description:Epidemiological data have linked vitamin D deficiency to the onset and severity of various cancers, including prostate cancer, and although in vitro studies have demonstrated anticancer activities for vitamin D, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically engineered Pten(i)pe-/- mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analog with reported anticancer activities. We show that this analog induces apoptosis in senescent PINs, normalizes extracellular matrix remodeling by stromal fibroblasts, and reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal cells expressing Krt8, Krt4, and Tacstd2 (termed luminal-C cells) is lost by such a treatment, antiapoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of PINs and the microenvironment to Gemini-72, and shed light on mechanisms that limit treatment's efficacy.

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Validation of differentially methylated DNA regions in colorectal precancerous lesions.

Project description:In this study, we validated 992 previously identified differentially methylated regions (DMRs) in colorectal precancerous lesions compared to adjacent normal mucosa in a new series of 59 prospectively collected lesions and matched normal tissue using targeted bisulfite sequencing. Strong differences in methylation level were observed across the full set of validated DMRs. Based on the mean methylation levels of a panel of 30 selected DMRs tumors could be accurately classified. We thus provide a large list of validated DNA markers to be exploited in the development of noninvasive, colorectal tumor screening assays.

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Genome wide DNA methylation profile in expressed prostatic secretions of normal and, benign and malignant prostatic lesions of diseased individuals

Project description:Genome wide DNA methylation profiling was done on expressed prostatic secretions (EPS) of normal individuals and dry-core needle biopsy samples of benign and malignant (Primary tumor) prostatic lesions. The Illumina Infinium 850k Infinium MethylationEPIC v 1.0 was used to obtain DNA methylation profiles across approximately 850,000 CpGs in EPS and prostatic lesion biopsy samples. Samples included 4 EPS of normal individuals, and 8 biopsy tissues of benign, and malignant lesions each of patient individuals.

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Project description:Prostate cancer (PCa) is a leading cause of cancer-related deaths. The slow evolution of prostatic precancerous lesions to malignant tumors provides a broad time-frame for strategies targeting disease emergence. To characterize prostatic intraepithelial neoplasia (PIN) progression, we conducted longitudinal studies on prostates of genetically-engineered Pten(i)pe- /- mice. We discovered that early PINs are hypoxic and that hypoxia-inducible factor 1 alpha (HIF1A) signaling is activated in luminal cells during disease progression. Luminal HIF1A enhances glucose metabolism and promotes a PIN-derived secretome that increases the recruitment of myeloid-derived suppressor cells, thus dampening immune surveillance. Moreover, pharmacological inhibition of HIF1A induces apoptosis in early PIN lesions, and slows the proliferation of late ones. Therefore, our study identifies HIF1A as a target for PCa prevention. Importantly, we also demonstrate that HIF1A signaling correlates with the emergence of prostatic luminal cells expressing TGM2, the expression of which predicts early relapse after primary intervention in PCa patients.

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Proteomics and Metabolomics unveils Codonopsis Radix ameliorates Gastric Precancerous Lesions via regulating energy metabolism

Project description:Modern pharmacology has proved that Codonopsis Radix and its active ingredients can treat stomach diseases by ameliorating gastrointestinal motility and regulating oxidase levels. However, the detailed molecular mechanism is still unclear. In this study, we systematically evaluated the pharmacodynamic effects of Codonopsis Radix in Gastric Precancerous Lesions animal models. Considering the combination of proteomics and metabolomics, we found that CR could significantly reversed the biological pathways related to energy metabolism which were disturbed by GPL model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix contained serum could ameliorate gastritis injury, and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in above cells.

2022-10-15 | PXD032714 | Pride

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