Pparg Drives Luminal Differentiation and Luminal Tumor Formation in the Urothelium

The urothelium is a crucial stratified epithelial barrier that protects the urinary tract. It consists of basal cells in the lower layers and intermediate and superficial cells in the luminal layer. These urothelial cells can be identified by their distinct gene expression patterns. Superficial cells are terminally differentiated, binucleated, post-mitotic cells that are responsible for the barrier function of the urothelium via the production of uroplakin proteins. Intermediate cells act as the progenitor cells for superficial cells during development, homeostasis, and after acute injury. Basal cells consist of two populations, K14-basal cells and K5-basal cells. K14- basal cells have been shown to be progenitors that can repopulate the urothelium after chronic injury and are the cells of origin that produce bladder cancer. Bladder cancer can be classified as basal subtype or luminal subtype. The basal subtype is generally immune infiltrated, aggressive, and invasive with a poor prognosis. The luminal subtype is generally immune poor, less aggressive, and non-invasive with a better prognosis compared to basal tumors. Pparg is a nuclear hormone receptor that has been described as a