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Chromatin Landscape of Normal Urothelial cells

ABSTRACT: Chromatin Landscape of Normal Urothelial cells

PROVIDER: PRJNA798080 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17648062.fastq.gz	Fastqsanger.gz
	SRR17648063.fastq.gz	Fastqsanger.gz
	SRR17648064.fastq.gz	Fastqsanger.gz
	SRR17648065.fastq.gz	Fastqsanger.gz
	SRR17648066.fastq.gz	Fastqsanger.gz

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Chromatin Landscape of Normal Urothelial cells

Project description:Describing the chromatin landscape of normal urothelial cells by ChIPseq analysis of 6 histones marks and 1 chromatin factor in 2 patient derived Normal Human Urothelial cells

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Single-cell profiling identifies rare normal mesenchymal-like urothelial cells associated with sarcomatoid urothelial carcinoma

Project description:The bladder urothelium is a stratified epithelium, categorized as basal, intermediate, and umbrella cells. While epithelial–mesenchymal transition is known to occur during bladder injury, regeneration, and sarcomatoid tumor formation, it remains unclear whether normal urothelial cells intrinsically possess a mesenchymal-like epithelial state. We analyzed scRNA-seq data of EPCAM+ urothelial cells from both mouse and human urothelium. Vimentin-positive cells were evaluated by immunostaining to determine their distribution in normal urothelial layers and sarcomatoid tumors. Here, we identified and characterized a rare population of mesenchymal-like urothelial cells, termed M-cells, representing ~1–3% of urothelial cells. M-cells co-express epithelial markers with mesenchymal and stemness genes and engage stem-associated transcriptional regulators. Lineage tracing with the Upk2-Cre mT/mG reporter mice confirmed their urothelial origin, excluding a fibroblast lineage. M-cells are enriched within the basal layer but present across all urothelial compartments. M-cells exhibit high transcriptional plasticity between basal cells and intermediate cells. In addition, we identified a 16-gene transcriptional signature uniquely expressed in M-cells but absent in fibroblasts. RNA deconvolution of MB49 tumors demonstrated strong enrichment of this signature, suggesting that MB49 tumors are more likely to represent sarcomatoid urothelial carcinoma rather than fibroblast-derived sarcoma. The clinical relevance of M-cells and the M-cell state was validated in primary human sarcomatoid tumors and their corresponding patient-derived xenografts. Together, these findings establish transcriptionally unique and rare mesenchymal-like cells within the normal urothelium as a novel highly plastic population with translational implications for both mouse and human sarcomatoid urothelial carcinoma.

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Project description:We have created 5-methylcytosine profiles for normal and malignant urothelial cells. Competitive hybridization of background and 5-methylcytosine enriched immunoprecipiated DNA fractions

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Project description:Activating mutations of FGFR3 are found in a high proportion of bladder tumours. The molecular consequences of FGFR3 mutation in urothelial cells and the mechanisms by which mutant FGFR3 may drive bladder tumourigenesis are largely unknown. We used expression arrays to identify downstream targets of mutant FGFR3 signalling in normal urothelial cells. TERT-immortalized normal urothelial cells stably transduced to express the most common FGFR3 mutation (S249C) were compared with control cells transduced with the empty vector (pFB).

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