p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia.

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.

• Authors: Jean-Christophe Pignon, Chiara Grisanzio, Yan Geng, Jiaxi Song, Ramesh A Shivdasani, Sabina Signoretti
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 110 Issue 20 Pg. 8105-10 (May 14 2013) ISSN: 1091-6490 [Electronic] United States
• PMID: 23620512 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphoproteins
• Trans-Activators
• Trp63 protein, mouse

Topics

• Animals
• Carcinoma, Squamous Cell (metabolism)
• Cell Line, Tumor
• Cell Lineage
• Colorectal Neoplasms (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knock-In Techniques
• Genotype
• Male
• Metaplasia (metabolism)
• Mice
• Mice, Transgenic
• Neoplastic Stem Cells (cytology, metabolism)
• Phosphoproteins (genetics, metabolism)
• Promoter Regions, Genetic
• Prostatic Neoplasms (genetics, metabolism)
• Protein Structure, Tertiary
• Stem Cells (cytology)
• Trans-Activators (genetics, metabolism)
• Urinary Bladder Neoplasms (genetics, metabolism)