p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia
| Autor: | Chiara Grisanzio, Ramesh A. Shivdasani, Jean-Christophe Pignon, Sabina Signoretti, Yan Geng, Jiaxi Song |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology medicine.medical_specialty Genotype Cre recombinase Mice Transgenic Biology Bladder Urothelium Mice Cancer stem cell Cell Line Tumor medicine Animals Cell Lineage Gene Knock-In Techniques Progenitor cell Promoter Regions Genetic Metaplasia Multidisciplinary Stem Cells Prostatic Neoplasms Biological Sciences Phosphoproteins Epithelium Protein Structure Tertiary Gene Expression Regulation Neoplastic medicine.anatomical_structure Urinary Bladder Neoplasms Amniotic epithelial cells Cancer research Carcinoma Squamous Cell Neoplastic Stem Cells Trans-Activators Female Stem cell Endoderm Colorectal Neoplasms |
| Popis: | The tumor protein p63 (p63), and more specifically the NH2-terminal truncated (ΔN) p63 isoform, is a marker of basal epithelial cells and is required for normal development of several epithelial tissues, including the bladder and prostate glands. Although p63-expressing cells are proposed to be the stem cells of the developing prostate epithelium and bladder urothelium, cell lineages in these endoderm-derived epithelia remain highly controversial, and rigorous lineage tracing studies are warranted. Here, we generated knock-in mice expressing Cre recombinase (Cre) under the control of the endogenous ΔNp63 promoter. Heterozygote ΔNp63 +/Cre mice were phenotypically normal and fertile. Cre-mediated recombination in ΔNp63 +/Cre ;ROSA26 EYFP reporter mice faithfully recapitulated the pattern of ΔNp63 expression and were useful for genetic lineage tracing of ΔNp63-expressing cells of the caudal endoderm in vivo. We found that ΔNp63-positive cells of the urogenital sinus generated all epithelial lineages of the prostate and bladder, indicating that these cells represent the stem/progenitor cells of those epithelia during development. We also observed ΔNp63 expression in caudal gut endoderm and the contribution of ΔNp63-positive cells to the stem/progenitor compartment of adult colorectal epithelium. Because p63 is a master regulator of stratified epithelial development, this finding provides a unique developmental insight into the cell of origin of squamous cell metaplasia and squamous cell carcinoma of the colon. |
| Databáze: | OpenAIRE |
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