2026-06-14T03:31:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/93192024-11-29T16:23:03Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Santos, Catarina P
author
Lapi, Eleonora
author
Martínez de Villarreal, Jaime
author
Álvaro-Espinosa, Laura
author
Fernández-Barral, Asunción
author
Barbáchano, Antonio
author
Dominguez, Orlando
author
Laughney, Ashley M
author
Megias Vazquez, Diego
author
Muñoz, Alberto
author
Real Arribas, Francisco
funder
Ministerio de Economía y Competitividad (España)
funder
Centro de Investigación Biomédica en Red - CIBERONC (Cáncer)
funder
Asociación Española Contra el Cáncer
2020-03-24T19:12:44Z
2020-03-24T19:12:44Z
2019-09-27
Nat Commun. 2019;10(1):4407.
10.1038/s41467-019-12307-1
2041-1723
2041-1723
Nature communications
31562298
http://hdl.handle.net/20.500.12105/9319
Understanding urothelial stem cell biology and differentiation has been limited by the lack of methods for their unlimited propagation. Here, we establish mouse urothelial organoids that can be maintained uninterruptedly for >1 year. Organoid growth is dependent on EGF and Wnt activators. High CD49f/ITGA6 expression features a subpopulation of organoid-forming cells expressing basal markers. Upon differentiation, multilayered organoids undergo reduced proliferation, decreased cell layer number, urothelial program activation, and acquisition of barrier function. Pharmacological modulation of PPARγ and EGFR promotes differentiation. RNA sequencing highlighted genesets enriched in proliferative organoids (i.e. ribosome) and transcriptional networks involved in differentiation, including expression of Wnt ligands and Notch components. Single-cell RNA sequencing (scRNA-Seq) analysis of the organoids revealed five clusters with distinct gene expression profiles. Together, with the use of γ-secretase inhibitors and scRNA-Seq, confirms that Notch signaling is required for differentiation. Urothelial organoids provide a powerful tool to study cell regeneration and differentiation.
eng
Urothelial organoids originating from Cd49fhigh mouse stem cells display Notch-dependent differentiation capacity
journal article
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