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Authors Colopy SA, Bjorling DE, Mulligan WA, Bushman W
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Journal Dev. Dyn. Volume: 243 Issue: 8 Pages: 988-98
Publish Date 2014 Aug
PubMed ID 24796293
PMC ID 4111772
Abstract

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.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.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.

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