In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells
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PROVIDER: PRJNA475133 | ENA |
REPOSITORIES: ENA
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Project description:The bladder’s remarkable regenerative capacity in response to injury had been thought to reside exclusively in its basal and intermediate cells. While examining consequences of DNA methyltransferase 1 (Dnmt1) inactivation in mouse embryonic bladder epithelium, we made the surprising discovery that Wolffian duct epithelial cells also support bladder regeneration. Conditional inactivation of Dnmt1 in mouse urethral and bladder epithelium triggered widespread apoptosis, depleted basal and intermediate bladder cells and disrupted Uroplakin protein expression. These events coincided with recruitment of Wolffian duct epithelial cells into Dnmt1 mutant urethra and bladder where they were reprogrammed to express bladder markers including FOXA1, Keratin 5, P63 and Uroplakin. This is the first evidence that Wolffian duct epithelial cells can be summoned in vivo to replace damaged bladder epithelium and function as a cell reservoir for bladder regeneration.
2018-07-19 | GSE115477 | GEO
Project description: Not available
| S-EPMC6099915 | biostudies-literature
Project description:We developed a method for the directed differentiation of hiPSCs into mature stratified bladder urothelium.
2019-07-30 | GSE131371 | GEO
Project description:Overactive bladder (OAB) syndrome is a condition that has four symptoms: urgency, urinary frequency, nocturia, and urge incontinence and negatively affects a patient’s life. Recently, it is considered that the urinary bladder urothelium is closely linked to pathogenesis of OAB. However, the mechanisms of pathogenesis of OAB at the molecular level remain poorly understood, mainly as a result of lack of modern molecular analysis. The goal of this study is to identify a potential target protein that could act as a predictive factor for effective diagnosis and aid in the development of therapeutic strategies for the treatment of OAB syndrome. We produced OAB in a rat model and performed the first proteomic analysis on the mucosal layer (urothelium) of the bladders of normal and OAB rats.
2018-02-09 | PXD007571 | Pride
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: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:The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing bladder. The central thesis is straightforward. The combination of microdissected and laser capture microdissection (LCM) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here represents the gene expression profiles of compartmental bladder tissues collected through laser capture microscopy. Experiment Overall Design: Bladders were isolated from newborn SMGA/EGFP transgenic mice, embedded in OCT, frozen and sectioned (8 microns). Detrusor, stroma and urothelium were isloated using laser capture microscopy. The caps were frozen on dry ice and stored at -80 degrees C until RNA was extracted for gene expression analysis. Laser captured and total RNA isolated for gene expression analysis using the Affymetrix MOE430 microarray chip.
2008-06-11 | E-GEOD-11221 | biostudies-arrayexpress
Project description:This experiment captures the expression of genes between two sites of human cartilage within the same patients to allow investigation of genomic responses to damage during osteoarthritis. Eight patients with symptomatic OA undergoing total knee replacement (n=8, age range 65-79 years, mean age 70.3) were used in this study. Cartilage from paired osteochondral samples were isolated from the intact PLC (posterior lateral condyle) and the damaged DMC (distal medial condyle) for RNA-seq analysis.
2016-04-06 | E-MTAB-4304 | biostudies-arrayexpress
Project description:Gene expression data of iPS clones before bladder urothelium differentiation
| PRJNA543410 | ENA
Project description:This data set shows results from tryptic digests of Porcine bladder urothelium. One tryptic digest was carried out after removal of both N-glycans and O-glycans. The other digest was performed without prior removal of glycans.
2017-04-20 | MSV000080973 | MassIVE