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Epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells

ABSTRACT: To gain a more depth knowledge of repressive epigenetic gene regulation in UCC, we have profiled H3K9m3 and H3K27m3 in normal and malignant urothelial cells. We matched these profiles to those 5-methylcytosine and gene expression. We hypothesized that differences represent pro-carcinogenic events within the urothelium. We identified a panel of genes with cancer specific epigenetic mediated aberrant expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31864 | GEO | 2011/09/20

SECONDARY ACCESSION(S): PRJNA155251

REPOSITORIES: GEO

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Epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells

Project description:To gain a more depth knowledge of repressive epigenetic gene regulation in UCC, we have profiled H3K9m3 and H3K27m3 in normal and malignant urothelial cells. We matched these profiles to those 5-methylcytosine and gene expression. We hypothesized that differences represent pro-carcinogenic events within the urothelium. We identified a panel of genes with cancer specific epigenetic mediated aberrant expression. Two repressive histone modifications (H3K9m3 and H3K27m3) , cytosine methylation and gene expression were compared between normal human urothelial cell line (NHU) and malignant urothelial cells (EJ and RT112).

2011-09-19 | E-GEOD-31864 | biostudies-arrayexpress

Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells [ChIP-Seq data]

Project description:We profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq in normal urothelial cells and cell lines representing non-invasive and invasive tumors. Two bladder cancer cell lines (RT112 and EJ/T24 from ATCC) and normal human urothelial (NHU) cells were treated according to standard ChIP-Seq protocols using antibodies against the histone modifications H3K9m3 and H3K27m3 (from Millipore). The sequencing reads were mapped against the human genome (GRCh37/hg19).

2011-08-03 | E-GEOD-31125 | biostudies-arrayexpress

Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells [ChIP-Seq data]

Project description:We profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq in normal urothelial cells and cell lines representing non-invasive and invasive tumors.

2011-08-03 | GSE31125 | GEO

Tobacco smoking transcriptional imprinting contributes to urothelial cancer

Project description:Smoking is a major risk factor for Urothelial carcinoma (UC). However the complex mechanisms, how smoking promotes carcinogenesis and tumour progression, remain obscure. A microarray based approached was therefore performed to detect the smoking derived gene expression alteration in non-malignant and malignant urothelial tissues from patients with superficial or invasive UC. Smoking enhanced cell migration and response to tissue damages. In non-malignant tissues smoking induced immune response and altered the cytoskeleton. In urothelial carcinoma, smoking altered extracellular and chromosome structures. Smoking affected tissues from patients with invasive carcinomamore strongly, up-regulating particularly growth factors and oncogenes in non-malignant tissue of patients with invasive but not with superficial carcinoma. In former smokers, comparable changes were seen in tissues form patients with invasive disease while they were minor or reversed in tissue of patients with superficial disease. Best but not complete tissue repair was suggestedfor non-malignant tissue from patients with superficial tumours. we used microarray techniques to define gene expression profile which may explain the contribution of smoking to urothelial carcinoma. Gene expression profiling using GeneChip HG-U133A Plus 2.0 (Affymetrix) was performed on non-malignant and carcinogenic urothelium from six patients with superficial and six with invasive urothelial carcinoma, each group including two current, former, and non-smokers.

2013-03-20 | E-GEOD-21142 | biostudies-arrayexpress

Single cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics.

Project description:Objectives: Much of the information to date in terms of subtypes and function of bladder urothelial cells were derived from anatomical location or by the expression of a small number of marker genes. To have a comprehensive map of the cellular anatomy of bladder urothelial cells, we performed single-cell RNA-sequencing to thoroughly characterize mouse bladder urothelium. Materials and methods: A total of 18,917 single cells from mouse bladder urothelium was analyzed by unbiased single-cell RNA sequencing. The expression of the novel cell marker was confirmed by immunofluorescence using urinary tract infections models. Results: Unsupervised clustering analysis identified 8 transcriptionally distinct cell subpopulations from mouse bladder urothelial cells. We discovered a novel type of bladder urothelial cells marked by Plxna4 that may be involved with host response and wound healing. We also found a group of basal-like cells labeled by ASPM that could be the progenitor cells of adult bladder urothelium. ASPM+ urothelial cells are significantly increased after injury by UPEC. In addition, specific transcription factors were found to be associated with urothelial cell differentiation. At the last, a number of interstitial cystitis/bladder pain syndrome-regulating genes were found differentially expressed among different urothelial cell subpopulations. Conclusions: Our study provides a comprehensive characterization of bladder urothelial cells, which is fundamental to understanding the biology of bladder urothelium and associated bladder disease.

2020-12-12 | GSE163029 | GEO

Global methylation in normal and malignant urothelial cells

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

2011-09-19 | E-GEOD-31865 | biostudies-arrayexpress

Global methylation in normal and malignant urothelial cells

Project description:We have created 5-methylcytosine profiles for normal and malignant urothelial cells.

2011-09-20 | GSE31865 | GEO

Kruppel-like factor 5 is Required for Urothelial Maturation

Project description:Kruppel-like transcription factor 5 (Klf5) is expressed during late embryogenesis in the forming murine bladder urothelium. Targeted disruption of the Klf5flox alleles by the ShhGfpCre transgene resulted in failure of the bladder urothelium to mature accompanied by hydronephrosis, hydroureter, and vesicoureteric reflux in all E18.5 fetuses. The bladder urothelium did not stratify nor did it express terminal differentiation markers characteristic of basal, intermediate, and umbrella cells including keratins 20, 14, and 5, and uroplakins. At E18.5, an ectopic alpha smooth muscle actin positive layer of cells was identified subjacent to the undifferentiated Klf5-deficient urothelium. The effects of Klf5 deficiency were unique to the urothelium since maturation of the epithelium comprising the bladder neck and urethra were unaffected by the lack of KLF5. mRNA microarray analysis of whole E14.5 control and Klf5 deficient bladders identified Ppar? and Grhl3 as putative downstream intermediary transcription factors that regulate urothelial maturation. Transient transfection assays demonstrated that KLF5 regulated expression of the mGrhl3 promoter. These observations show that alterations in maturation of the bladder urothelium alone are sufficient to induce bladder dysfunction leading to prenatal hydronephrosis. Total RNA from E14.5 whole bladders isolated from Klf5D/D and Klf5+/+ShhGfpCre+ embryos (n=3 samples/genotype, each sample a pool of two bladders) was isolated using the Qiagen MicroRNA Kit. The cDNA was then hybridized according to the manufacturer’s protocol to the Affymetrix Mouse Gene 1.0 ST Array

2011-08-01 | E-GEOD-27014 | biostudies-arrayexpress

Kruppel-like factor 5 is Required for Urothelial Maturation

Project description:Kruppel-like transcription factor 5 (Klf5) is expressed during late embryogenesis in the forming murine bladder urothelium. Targeted disruption of the Klf5flox alleles by the ShhGfpCre transgene resulted in failure of the bladder urothelium to mature accompanied by hydronephrosis, hydroureter, and vesicoureteric reflux in all E18.5 fetuses. The bladder urothelium did not stratify nor did it express terminal differentiation markers characteristic of basal, intermediate, and umbrella cells including keratins 20, 14, and 5, and uroplakins. At E18.5, an ectopic alpha smooth muscle actin positive layer of cells was identified subjacent to the undifferentiated Klf5-deficient urothelium. The effects of Klf5 deficiency were unique to the urothelium since maturation of the epithelium comprising the bladder neck and urethra were unaffected by the lack of KLF5. mRNA microarray analysis of whole E14.5 control and Klf5 deficient bladders identified Ppar-gamma and Grhl3 as putative downstream intermediary transcription factors that regulate urothelial maturation. Transient transfection assays demonstrated that KLF5 regulated expression of the mGrhl3 promoter. These observations show that alterations in maturation of the bladder urothelium alone are sufficient to induce bladder dysfunction leading to prenatal hydronephrosis.

2011-08-02 | GSE27014 | GEO

Genome-wide DNA methylation analysis of non-cancerous urothelium obtained from patients with urothelial carcinomas and corresponding cancerous tissue

Project description:The aim of this study was to establish criteria for carcinogenetic risk estimation in the urothelium. Forty-six samples of non-cancerous urothelium showing no remarkable histological findings obtained from patients with urothelial carcinomas (N), and 46 samples of the corresponding cancerous tissue (T), i.e. 92 tissue samples in total, were analyzed. Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation 450K BeadChip.

2019-08-15 | GSE111933 | GEO

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