Mendelsohn Group (GUDMAP2)
The urinary outflow tract, including the renal pelvis, ureters, bladder and upper urethra, is lined by a specialized stratified epithelium called the urothelium, composed of a basal layer, an intermediate layer and a superficial layer consisting of umbrella cells. Umbrella cells are large multinucleated cells that are specialized for synthesis and trafficking of Uroplakins, a family of secreted proteins that assemble into the crystallin plaque lining the apical surface of the urothelium that generates a leak-proof barrier between the urine and the blood.
The urothelium can be rendered dysfunctional by damage, or disease, including interstitial cystitis, inflammation and UTI, but at present there is no way to repair/regenerate this tissue. In addition, the urothelium is thought to be a source of stem/progenitor cells that give rise to different forms of bladder cancer. One impediment to progress has been the paucity of markers distinguishing urothelial sub-types including progenitors.
As part of GUDMAP2, we will generate a collection of genetic markers specific for urothelial sub-populations beginning with those that we have defined using transgenic and lineage-tagged mouse models expressing RFP or GFP. In addition to umbrella cells and basal cells, we have been able to define a novel cell type that resides in the intermediate layer that is a likely umbrella cell progenitor. Flow sorted cell populations will be genetically profiled by the Potter/Aronow labs using RNA-Seq. Validated candidates will be assessed to determine their distribution in the mouse and human urothelium, using in situ hybridization and immunohistochemistry.
Grant number: 5U01DK094530