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CD49f labels an organoid-forming mouse urothelial cell population with stem cell features

AuthorsSantos, Catarina P.; Lapi, Eleonora; Álvaro, Laura; Barbáchano, Antonio ; Barral, Asunción; Muñoz Terol, Alberto ; Real, Francisco X.
Issue Date2017
Citation15th Meeting of the International Bladder Cancer Network (2017)
Abstract[Objectives]: Urothelial bladder cancer (UBC) is a heterogeneous disease. Currently, it is thought that indolent papillary tumors arise from committed progenitors whereas aggressive muscle-invasive tumors arise from cells in the basal layer. However, our understanding of the molecular mechanisms involved in urothelial cell differentiation and maintenance is incomplete. Therefore, the aim of this study is to develop cultures for normal mouse urothelial organoids (NMU-o) and to exploit in order to better understand urothelial biology and tumorigenesis. [Material and methods]: We developed methods to establish and expand NMU-o, and to identify cells with stem cell features. We subsequently used immunofluorescence and RT-qPCR to characterize NMU-o at the molecular level. [Results]: We have established methods to maintain NMU-o for more than one year uninterruptedly in culture. Our results indicate that: Wnt pathway activators (WNT3A and RSPO1) and epidermal growth factor are essential for NMU-o proliferation; CD49f, a marker of urothelial basal cells, identifies the population of NMU-o forming cells; under proliferation, NMU-o cultures express mainly markers of stem and basal cells such as CD44, KRT14 and KRT5; and under differentiation, NMU-o cultures acquire a “lumen-like” phenotype with features characteristic of the suprabasal layers of the urothelium with high expression of uroplakins. However, our cultures do not contain KRT20-expressing umbrella cells. [Conclusions]: We provide conclusive evidence that the Cd49fþ subpopulation contains urothelial stem cells. This in vitro model constitutes a powerful tool to study urothelial cell biology and to decipher the molecular pathways involved in bladder cancer. Moreover, it provides the basis for the development of methods for the culture of normal and malignant urothelial organoids as platforms for functional genomics and drug screening.
DescriptionResumen del póster presentado al 15th Meeting of the International Bladder Cancer Network (IBCN), celebrado en Lisboa (Portugal) del 21 al 23 de octubre de 2017.
Appears in Collections:(IIBM) Comunicaciones congresos
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