The human urothelium consists of multiple clonal units, each maintained by a stem cell

• DOI: 10.1002/path.2945
• Publication Date: 2011-05-30T13:15:32Z
• Authors: Nadine T Gaisa; Trevor A Graham; Stuart AC McDonald; Sagrario Cañadill...; Richard Poulsom; Axel Heidenreich; Gerhard Jakse; Paul J Tadrous; Ruth Knuechel; Nicholas A Wright
• Keywords: Urothelial Cell; Stem cell marker

Abstract Little is known about the clonal architecture of human urothelium. It likely that urothelial stem cells reside within basal epithelial layer, yet lineage tracing from a single cell as means to show presence has never been performed. Here, we identify clonally related areas bladder mucosa in order visualize fields maintained by founder/stem cell. Sixteen frozen cystectomy specimens were serially sectioned. Patches deficient for mitochondrially encoded enzyme cytochrome c oxidase (CCO) identified using dual‐colour histochemistry. To these patches represent proliferations, small CCO‐proficient and ‐deficient individually laser‐capture microdissected entire mitochondrial genome (mtDNA) each area was PCR amplified sequenced mtDNA mutations. Immunohistochemistry performed different layers urothelium adjacent mesenchyme. CCO‐deficient could be observed normal all specimens. The two‐dimensional length negative varied 2–3 (about 30 µm) 4.7 mm. Each patch contained an identical somatic mutation, indicating unit. mature differentiation stages present urothelium, suggesting Our results demonstrate contains cell‐derived units actively replenish during ageing. size unit attributable broadly distributed, replacement one clone another. Copyright © 2011 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.