ArticlePloS one2010
All-trans retinoic acid directs urothelial specification of murine embryonic stem cells via GATA4/6 signaling mechanisms.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Trial
- Urothelial-lineage master transcription factor hub proteomics shows mechanisms impeding urothelial cancer cell differentiation.bioRxiv : the preprint server for biology · 2026Article
- Vitamin A-Enriched Diet Increases Urothelial Cell Proliferation by Upregulating Itga3 and Areg After Cyclophosphamide-Induced Injury in Mice.Molecular nutrition & food research · 2025Article
- Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer.Nature communications · 2024Article
- Article
- Dietary Vitamin A Affects the Function of Incretin-Producing Enteroendocrine Cells in Male Mice Fed a High-Fat Diet.The Journal of nutrition · 2023Article
- Insights into vitamin A in bladder cancer, lack of attention to gut microbiota?Frontiers in immunology · 2023Review
- Generation of Urothelial Cells from Mouse-Induced Pluripotent Stem Cells.International journal of stem cells · 2022Article
- Sources, Selection, and Microenvironmental Preconditioning of Cells for Urethral Tissue Engineering.International journal of molecular sciences · 2022Review
- Development, regeneration and tumorigenesis of the urothelium.Development (Cambridge, England) · 2022Review
- Modeling different types of diabetes using human pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021Review
- Vitamin A Rich Diet Diminishes Early Urothelial Carcinogenesis by Altering Retinoic Acid Signaling.Cancers · 2020Article
- Application of Adult and Pluripotent Stem Cells in Interstitial Cystitis/Bladder Pain Syndrome Therapy: Methods and Perspectives.Journal of clinical medicine · 2020Review
- Crosstalk Between Retinoic Acid and Sex-Related Genes Controls Germ Cell Fate and Gametogenesis in Medaka.Frontiers in cell and developmental biology · 2020Article
- Regenerative and engineered options for urethroplasty.Nature reviews. Urology · 2019Review
- Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2.International journal of molecular sciences · 2019Article
- Tissue engineering for urinary tract reconstruction and repair: Progress and prospect in China.Asian journal of urology · 2018Review
- Squamous differentiation in patients with superficial bladder urothelial carcinoma is associated with high risk of recurrence and poor survival.BMC cancer · 2017Article
- Heterarchy of transcription factors driving basal and luminal cell phenotypes in human urothelium.Cell death and differentiation · 2017Article
- Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification.The Journal of pathology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The urinary bladder and associated tract are lined by the urothelium, a transitional epithelium that acts as a specialized permeability barrier that protects the underlying tissue from urine via expression of a highly specific group of proteins known as the uroplakins (UP). To date, our understanding of the developmental processes responsible for urothelial differentiation has been hampered due to the lack of suitable models. In this study, we describe a novel in vitro cell culture system for derivation of urothelial cells from murine embryonic stem cells (ESCs) following cultivation on collagen matrices in the presence all trans retinoic acid (RA). Upon stimulation with micromolar concentrations of RA, ESCs significantly downregulated the pluripotency factor OCT-4 but markedly upregulated UP1A, UP1B, UP2, UP3A, and UP3B mRNA levels in comparison to naïve ESCs and spontaneously differentiating controls. Pan-UP protein expression was associated with both p63- and cytokeratin 20-positive cells in discrete aggregating populations of ESCs following 9 and 14 days of RA stimulation. Analysis of endodermal transcription factors such as GATA4 and GATA6 revealed significant upregulation and nuclear enrichment in RA-treated UP2-GFP+ populations. GATA4-/- and GATA6-/- transgenic ESC lines revealed substantial attenuation of RA-mediated UP expression in comparison to wild type controls. In addition, EMSA analysis revealed that RA treatment induced formation of transcriptional complexes containing GATA4/6 on both UP1B and UP2 promoter fragments containing putative GATA factor binding sites. Collectively, these data suggest that RA mediates ESC specification toward a urothelial lineage via GATA4/6-dependent processes.
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