A population of progenitor cells in the basal and intermediate layers of the murine bladder urothelium contributes to urothelial development and regeneration

Dev Dyn. 2014 Aug;243(8):988-98. doi: 10.1002/dvdy.24143. Epub 2014 May 19.


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.

Keywords: bacteria; cystitis; progenitor; urinary injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Female
  • Humans
  • Pregnancy
  • Stem Cells / cytology*
  • Stem Cells / physiology
  • Urinary Bladder / cytology*
  • Urothelium / cytology*