TAp63 prevents premature aging by promoting adult stem cell maintenance.
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 (TAp63(fl/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.
Su
Xiaohua
X
Department of Molecular and Cellular Oncology, Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Paris
Maryline
M
Gi
Young Jin
YJ
Tsai
Kenneth Y
KY
Cho
Min Soon
MS
Lin
Yu-Li
YL
Biernaskie
Jeffrey A
JA
Sinha
Satrajit
S
Prives
Carol
C
Pevny
Larysa H
LH
Miller
Freda D
FD
Flores
Elsa R
ER
D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology*; D019588:Aging, Premature / Q000209:etiology* / Q000473:pathology; D000818:Animals; D016922:Cellular Senescence; D004249:DNA Damage; D020405:Dermis / Q000166:cytology*; D000078404:Epidermal Cells; D016158:Genes, p53; D042822:Genomic Instability; D018859:Hair Follicle / Q000166:cytology; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D015595:Skin Aging / Q000235:genetics / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics
D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse