@article{255ac291d7ed47da8f895881b5bf5820,
title = "TAp63 Prevents Premature Aging by Promoting Adult Stem Cell Maintenance",
abstract = "The cellular mechanisms that regulate the maintenance of adult tissue stem cells are still largely unknown. We show here that the p53 family member, TAp63, is essential for maintenance of epidermal and dermal precursors and that, in its absence, these precursors senesce and skin ages prematurely. Specifically, we have developed a TAp63 conditional knockout mouse and used it to ablate TAp63 in the germline (TAp63-/-) or in K14-expressing cells in the basal layer of the epidermis (TAp63fl/fl;K14cre+). TAp63-/- mice age prematurely and develop blisters, skin ulcerations, senescence of hair follicle-associated dermal and epidermal cells, and decreased hair morphogenesis. These phenotypes are likely due to loss of TAp63 in dermal and epidermal precursors since both cell types show defective proliferation, early senescence, and genomic instability. These data indicate that TAp63 serves to maintain adult skin stem cells by regulating cellular senescence and genomic stability, thereby preventing premature tissue aging.",
keywords = "STEMCELL",
author = "Xiaohua Su and Maryline Paris and Gi, {Young Jin} and Tsai, {Kenneth Y.} and Cho, {Min Soon} and Lin, {Yu Li} and Biernaskie, {Jeffrey A.} and Satrajit Sinha and Carol Prives and Pevny, {Larysa H.} and Miller, {Freda D.} and Flores, {Elsa R.}",
note = "Funding Information: This work was supported by grants to E.R.F. from the American Cancer Society (RSG-07-082-01-MGO), March of Dimes (Basil O'Connor Scholar), Susan G. Komen Foundation (BCTR600208), Leukemia and Lymphoma Society/Hildegarde D. Becher Foundation, and NCI Cancer Center Core Grant (CA-16672) (U.T. M.D. Anderson Cancer Center) and by grants to F.D.M. from the Canadian Institutes of Health Research (MOP-64211) and HHMI. E.R.F. is a scholar of the Rita Allen Foundation and the V Foundation for Cancer Research. F.D.M. is a Canada Research Chair and an HHMI International Research Scholar. We gratefully acknowledge the work of Jan Parker-Thornburg, the Genetically Engineered Mouse Facility, and the T.C. Hsu Molecular Cytogenetics Core at M.D. Anderson (funded by NCI no. CA16672). We would also like to acknowledge Wei Zhang for technical assistance, Paul Lambert and Denis Lee for J2-3T3 feeder cells, Dennis Roop for K14 antibody, Alea Mills for p63 −/− mice, Elaine Fuchs for advice on wound-healing assays, and David Kaplan and Chi-chung Hui for advice and input with regard to the manuscript. ",
year = "2009",
month = jul,
day = "2",
doi = "10.1016/j.stem.2009.04.003",
language = "English (US)",
volume = "5",
pages = "64--75",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",
}