title: A population of progenitor cells in the basal and intermediate layers of the murine bladder urothelium contributes to urothelial development and regeneration.
abstract: BACKGROUND
  Homeostatic maintenance and repair of the bladder urothelium has been attributed to proliferation of keratin 5-expressing basal cells (K5-BC) with subsequent differentiation into superficial cells. Recent evidence, however, suggests that the intermediate cell layer harbors a population of progenitor cells. We use label-retaining cell (LRC) methodology in conjunction with a clinically relevant model of uropathogenic Escherichia coli (UPEC)-induced injury to characterize urothelial ontogeny during development and in response to diffuse urothelial injury.
  
  
  RESULTS
  In the developing urothelium, proliferating cells were dispersed throughout the K5-BC and intermediate cells layers, becoming progressively concentrated in the K5-BC layer with age. When 5-bromo-2-deoxyuridine (BrdU) was administered during urothelial development, LRCs in the adult were found within the K5-BC, intermediate, and superficial cell layers, the location dependent upon time of labeling. UPEC inoculation resulted in loss of the superficial cell layer followed by robust proliferation of K5-BCs and intermediate cells. LRCs within the K5-BC and intermediate cell layers proliferated in response to injury.
  
  
  CONCLUSIONS
  Urothelial development and regeneration following injury relies on proliferation of K5-BC and intermediate cells. The existence and proliferation of LRCs within both the K5-BC and intermediate cell layers suggests the presence of two populations of urothelial progenitor cells.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Colopy
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bjorling
authors.forename: William A
authors.initials: WA
authors.lastname: Mulligan
authors.forename: Wade
authors.initials: W
authors.lastname: Bushman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D001743:Urinary Bladder / Q000166:cytology*; D019459:Urothelium / Q000166:cytology*
keywords: bacteria; cystitis; progenitor; urinary injury