Abstract: The urinary bladder is lined by a multilayered transitional epithelium known as the urothelium. It consists of a fully differentiated superficial cell layer (serving as a protective barrier to toxic metabolites in the urine), a basal cell layer (thought to harbor progenitor cells for the more superficial cell layers), and an intermediate cell layer, which is highly variable in thickness and thought to serve as a transitional phenotype between the basal cells and differentiated superficial cells.
The urothelium is a self-renewing tissue with a slow turnover rate during normal physiological conditions but a remarkable capacity to regenerate in the face of injury. Following urothelial destruction, the bladder is able to regenerate the urothelium in a matter of 1-2 weeks. Surprisingly, the cellular and molecular mechanisms underlying this remarkable shift in urothelial turnover are poorly defined. Though slow-cycling progenitor cells have been characterized in several organs, the location of progenitor cells in the urinary bladder remains elusive.
We studied the ontogeny of the urothelium during development and identified 2 separate populations of slow-cycling cells, one within cytokeratin 5-positive basal cells and one within cytokeratin 5-negative cells. We then characterized the healing response of the urothelium in a model of uropathogenic Escherichia coli-induced urothelial injury, and showed that both basal cells and intermediate cells contribute to the reparative process. Further, we showed that slow-cycling cells, labeled during development, persist into adulthood and proliferate in response to urothelial injury. We describe a unique temporal ontogeny of the bladder urothelium and propose the existence of two separate populations of progenitor cells that are independently recruited for rapid urothelial regeneration in the face of diffuse urothelial injury.
Authors: Sara A. Colopy, Dale E. Bjorling, Bill Mulligan, Wade A. Bushman