KRT14 marks a subpopulation of bladder basal cells with pivotal role in regeneration and tumorigenesis

• Published in: Nature communications 2016-06, Vol.7 (1), p.11914-11, Article 11914
• Main Authors: Papafotiou, George, Paraskevopoulou, Varvara, Vasilaki, Eleni, Kanaki, Zoi, Paschalidis, Nikolaos, Klinakis, Apostolos
• Format: Article
• Language: English
• Subjects: 13/100; 13/106; 14; 14/19; 42/41; 631/136/2441; 631/136/532/489; 631/67/589; 64/60; 692/420/755; Animals; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical research; Bladder cancer; Cell Differentiation; Cell Lineage - drug effects; Cell Lineage - genetics; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cells; Cyclophosphamide - toxicity; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Gene Expression; Genes, Reporter; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humanities and Social Sciences; Humans; Keratin; Keratin-14 - genetics; Keratin-14 - metabolism; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Male; Mice; Mice, Transgenic; multidisciplinary; Red Fluorescent Protein; Regeneration - genetics; Science; Science (multidisciplinary); Tissue engineering; Tumorigenesis; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Urinary Bladder - pathology; Urothelium - drug effects; Urothelium - metabolism; Urothelium - pathology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11914

The urothelium is a specialized epithelium that lines the urinary tract. It consists of three different cell types, namely, basal, intermediate and superficial cells arranged in relatively distinct cell layers. Normally, quiescent, it regenerates fast upon injury, but the regeneration process is not fully understood. Although several reports have indicated the existence of progenitors, their identity and exact topology, as well as their role in key processes such as tissue regeneration and carcinogenesis have not been clarified. Here we show that a minor subpopulation of basal cells, characterized by the expression of keratin 14, possesses self-renewal capacity and also gives rise to all cell types of the urothelium during natural and injury-induced regeneration. Moreover, these cells represent cells of origin of urothelial cancer. Our findings support the hypothesis of basally located progenitors with profound roles in urothelial homoeostasis. It is unclear whether there is a progenitor/stem cell in the basal layer of the urothelium in the bladder. Here, the authors identify Keratin14 positive cells that can regenerate the bladder in both a natural and injury-induced manner, and following neoplastic transformation, can give rise to tumours.