KRT14 marks a subpopulation of bladder basal cells with pivotal role in regeneration and tumorigenesis.
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.
Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
George
G
Papafotiou
Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Varvara
V
Paraskevopoulou
Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Eleni
E
Vasilaki
Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Zoi
Z
Kanaki
Laboratory of Cellular Immunology, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Nikolaos
N
Paschalidis
Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Apostolos
A
Klinakis
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053547:Keratin-14 / Q000235:genetics* / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012038:Regeneration / Q000235:genetics*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000097573:Red Fluorescent Protein
D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D049452:Green Fluorescent Proteins; D053547:Keratin-14; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C507446:Krt14 protein, mouse