Genome-wide DNA methylation analysis of non-cancerous urothelium obtained from patients with urothelial carcinomas and corresponding cancerous tissue
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ABSTRACT:
PROVIDER: PRJNA438600 | ENA |
REPOSITORIES: ENA
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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
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
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.
2026-07-30 | GSE330882 | GEO
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.
2026-07-30 | GSE330902 | GEO
Project description:Epithelial stem cells are essential for lineage specification, tissue renewal, and regeneration. Here we show that ureterovesical junction (UVJ) of urinary tract harbors a major cluster of label-retaining urothelial cells that exhibit organoid-forming activities. During lineage-tracing, these Foxa2-expressing UVJ urothelial cells renew ureteral urothelium, but do not migrate into the bladder during homeostasis or mild bladder injury. Upon mechanical and chemical denudation of bladder urothelium, UVJ cells migrate rapidly into the bladder to replace bladder urothelium. This reepithelization also occurs during combination chemotherapies and severe bladder infection. Common to these injury repair processes is the early-phase and selective phosphorylation of TRKA and AKT which drives urothelial proliferation and differentiation. Nascent bladder urothelial cells derived from UVJ express both UVJ and bladder urothelial markers, signifying active remodeling influenced by intrinsic and extrinsic factors. Modulating the activities of UVJ cells may enhance bladder urothelial regeneration and combat challenging bladder diseases.
2026-07-30 | GSE337018 | GEO
Project description:Urothelium forms a distensible yet impermeable barrier, senses and transduces stimuli, and defends the urinary tract from mechanical, chemical and bacterial injuries. Biochemical and genetic labeling studies support the existence of one or more progenitor populations with the capacity to rapidly regenerate the urothelium following injury, but slow turnover, a low mitotic index, and inconsistent methodologies obscure progenitor identity. The progenitor properties of basal Keratin 5 urothelial cells (K5-UC) have been previously investigated, but those studies focused on embryonic or adult bladder urothelium. Urothelium undergoes desquamation and apoptosis after birth, which requires postnatal proliferation and restoration. Therefore, we mapped the fate of bladder K5-UCs across postnatal development/maturation and following administration of cyclophosphamide to measure homeostatic and reparative progenitor capacities, respectively. In vivo studies demonstrate that basal K5-UCs are age-restricted progenitors in neonates and juveniles, but not in adult mice. Neonatal K5-UCs retain a superior progenitor capacity in vitro, forming larger and more differentiated urothelial organoids than adult K5-UCs. Accordingly, K5-UC transcriptomes are temporally distinct, with enrichment of transcripts associated with cell proliferation and differentiation in neonates. Induction of urothelial proliferation is sufficient to restore adult K5-UC progenitor capacity. Our findings advance the understanding of urothelial progenitors and support a linear model of urothelial formation and regeneration, which may have significant impact on therapeutic development or tissue engineering strategies.
2024-01-03 | GSE248463 | GEO
Project description:We made use of the fact that patients with non-muscle invasive tumors show frequent local recurrences and multiple tumors to study re-initiation of tumor growth from the same urothelium. By extensive genomic analyses we show that tumors from the same patient are clonal. We show that gross genomic chromosomal aberrations may appear abruptly and disappear with no transitional stages being observed. By analysis of incompatible changes i.e., genomic alterations that cannot be reversed, we show that almost all tumors from a single patient show such changes, thus the tumors cannot have originated from each other. As recurrent tumors share both genomic alterations and driver gene mutations, these must have been present in the histologically normal urothelium in periods with no tumor growth. We present a model that includes a growing and genomically evolving field of urothelial cells that occasionally, and locally, produce bursts of cellular growth leading to overt tumors. This gene expression data was used to check the molecular subtypes based on Lund taxonomy (LundTax) in the recurring urothelial carcinomas.
2020-03-13 | GSE146870 | GEO
Project description:Peroxisome Proliferator-Activated Receptor-gamma (PPARG) is a nuclear hormone receptor that was originally described as a master regulator of adipogenesis but could also promote cellular differentiation in a number of epithelium. PPARG also serves as an important regulator in anti-inflammatory activity after a variety of injuries, acting in part by antagonizing the NF-kB pathway. Moreover, the expression of PPARG is strongly down regulated in the basal subtype of bladder cancer, suggesting that its removal might be essential in tumorigenesis. In urothelial cells, it has been shown that PPARG promotes urothelial differentiation in vitro, but its function in vivo remains unexplored. The urothelium is a stratified epithelium that serves as a barrier between the urinary tract and blood. It consists of terminally differentiated umbrella cells, intermediate cells which serve as umbrella cell progenitors; and unipotent basal cells. To determine the role of PPARG in vivo, we used Cre-Lox recombination to conditionally delete the Pparg gene in the mouse urothelium using the ShhCre driver, which drives recombination in basal and intermediate cells, and their respective daughters. Interestingly, ShhCre;Ppargfl/fl mutants lack umbrella and intermediate cells, but have an abnormal cell population negative for classical urothelial markers instead. Furthermore, we observed an increase of KRT14+ population in the basal compartment and squamous features in the mutant urothelium. Expression profile analysis suggested PPARG regulates metabolism, urothelial differentiation and innate immune response. We further challenged the Pparg mutant urothelium with acute injury. In wild type animals, urinary tract infection (UTI) with uropathogenic E.coli results in a transient innate immune response, followed by a completed regernation within 2 weeks. When ShhCre;Ppargfl/fl mutants were challenged with urinary tract infection, the innate immune response was not resolved even after several weeks and the Pparg ablated urothelium exhibited squamous metaplasia. RNAseq data suggested that PPARG plays a role in regulating squmous differentiation and NFkB signial pathway. Together these findings suggest that PPARG is essential for the normal differentiation of the urothelium and is a potent regulator of the inflammatory response after UTI. Understanding the link between the loss of PPARG, chronic inflammation and tumorigenesis in the urothelium could shed light on the urothelial differentiation network and pave the way for the development of therapeutic approaches to various urinary diseases.
2019-07-25 | GSE123779 | GEO
Project description:To identify ythe the functional roles and the pathophysiological contributions of coding genes and noncoding RNAs in human colorectal carcinogenesis, we analysed the differenial expression of genes and noncoding RNAs in colorectal cancer tissues and the corresponding non-cancerous tissues.
2024-05-01 | GSE244968 | GEO
Project description:To identify the the functional roles and the pathophysiological contributions of the mRNA m6A modification in human colorectal carcinogenesis, we analysed the profile the landscape of the mRNA m6A modification in colorectal cancer tissues and the corresponding non-cancerous tissues.
2024-05-01 | GSE247632 | GEO