GSE115477
In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells
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. Overall design: Bladder urothelium were separated from stroma tissues and profiled by RNA-seq. Total 14 samples, from E15.5 embryos with three different genotypes ( including conditional Dnmt1 KO in the bladder urothelium, detailed in sample list characteristics: genotypes)