期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2013
卷号：110
期号：20
页码：8105-8110
DOI：10.1073/pnas.1221216110
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The tumor protein p63 (p63), and more specifically the NH2-terminal truncated ({Delta}N) 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{Delta} Np63 promoter. Heterozygote{Delta} Np63+/Cre mice were phenotypically normal and fertile. Cre-mediated recombination in{Delta} Np63+/Cre;ROSA26EYFP reporter mice faithfully recapitulated the pattern of {Delta}Np63 expression and were useful for genetic lineage tracing of {Delta}Np63-expressing cells of the caudal endoderm in vivo. We found that {Delta}Np63-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 {Delta}Np63 expression in caudal gut endoderm and the contribution of {Delta}Np63-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.
