Urothelial organoids originating from Cd49f^high mouse stem cells display Notch-dependent differentiation capacity.

ABSTRACT: 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 expre

SUBMITTER: Santos CP 

PROVIDER: S-EPMC6764959 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature