p63 identifies keratinocyte stem cells
By G. Pellegrini, E. Dellambra, O. Golisano, E. Martinelli, I. Fantozzi, S. Bondanza, D. Ponzin, F. McKeon, M. De Luca. Proceedings of the National Academy of Sciences of the United States of America, 2001
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The proliferative compartment of stratified squamous epithelia consists of stem and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant in putative epidermal stem cells than in TA cells, but no polypeptide confined to the stem cells has yet been identified. Here we show that the p63 transcription factor, a p53 homologue essential for regenerative proliferation in epithelial development, distinguishes human keratinocyte stem cells from their TA progeny. Within the cornea, nuclear p63 is expressed by the basal cells of the limbal epithelium, but not by TA cells covering the corneal surface. Human keratinocyte stem and TA cells when isolated in culture give rise to holoclones and paraclones, respectively. We show by clonal analysis that p63 is abundantly expressed by epidermal and limbal holoclones, but is undetectable in paraclones. TA keratinocytes, immediately after their withdrawal from the stem cell compartment (meroclones), have greatly reduced p63, even though they possess very appreciable proliferative capacity. Clonal evolution (i.e., generation of TA cells from precursor stem cells) is promoted by the sigma isoform of the 14-3-3 family of proteins. Keratinocytes whose 14-3-3σ has been down-regulated remain in the stem cell compartment and maintain p63 during serial cultivation. The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis.
Subfields: Molecular Biology, Oncology, Radiology, Nuclear Medicine and Imaging
View Paper: https://www.semanticscholar.org/paper/981e267704e4280ffb30b055dfe6f473c5976ca1
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Citations in the corpus
- Positive and negative regulation of ΔN-p63 promoter activity by p53 and ΔN-p63-α contributes to differential regulation of p53 target genes (2003, background): “In a developmental model of corneal keratinocytes, DN-p63 isoforms maintain multipotency and loss of DN-p63-a mRNA correlates with transient amplification of limbal epithelia (Pellegrini et al., 2001).”
- p63 is the molecular switch for initiation of an epithelial stratification program. (2004, background): “It has been proposed that p63may play a pivotal role in maintaining the stem cell population in an already committed stratified epithelium (Yang et al. 1999; Pellegrini et al. 2001).”
- Getting under the skin of epidermal morphogenesis (2002, background): “cgi?l=7157">p53 homologue that is expressed throughout the basal layer of the epidermi”