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p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2013 May 14; Vol. 110 (20), pp. 8105-10. Date of Electronic Publication: 2013 Apr 25. - Publication Year :
- 2013
-
Abstract
- 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.
- Subjects :
- Animals
Carcinoma, Squamous Cell metabolism
Cell Line, Tumor
Cell Lineage
Colorectal Neoplasms genetics
Female
Gene Knock-In Techniques
Genotype
Male
Metaplasia metabolism
Mice
Mice, Transgenic
Neoplastic Stem Cells metabolism
Phosphoproteins genetics
Promoter Regions, Genetic
Prostatic Neoplasms genetics
Protein Structure, Tertiary
Stem Cells cytology
Trans-Activators genetics
Urinary Bladder Neoplasms genetics
Colorectal Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Neoplastic Stem Cells cytology
Phosphoproteins metabolism
Prostatic Neoplasms metabolism
Trans-Activators metabolism
Urinary Bladder Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 110
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 23620512
- Full Text :
- https://doi.org/10.1073/pnas.1221216110