Re: Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder

The regeneration of multilayered urinary bladder epithelium that consists of umbrella cells, intermediate cells, and basal cells that shift from a state of near quiescence to being highly proliferative in response to injury was the focus of the in vitro and in vivo investigations of Shin et al. In contrast to bladder epithelia, the epithelia of other organs, such as the intestine, regenerate constantly and without an injury-response stimulus. The proliferative response to simulated bacterial infection or chemical injury of the murine bladder was induced and the suspected regulatory signaling between the basal cells of the urothelium and the underlying stromal cells was examined in vitro. Hereby, it was impressively shown that within the basal-cell population, a multipotent stem cell exists that is capable of regenerating all cell types within the urothelium. Not only was the putative urothelial stem cell identified via the expression of secreted sonic hedgehog (Shh) protein, Wnt signaling was confirmed to affect the cell's proliferative behavior. Due to injury, Shh expression was upregulated in basal cells while increasing stromal expression of Wnt protein signals. The induced signal feedback circuited and the associated increased cell proliferation appeared to be required for restoration of the urothelial function. In addition, the regenerative potential of the urothelial stem cells was demonstrated when single Shh-expressing cells formed cyst-like organoids in Matrigel cultures.