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G Pellegrini, E Dellambra, E Martinelli, CE Traverso, P Rama, P Lacal, M De Luca; Telomerase is Sufficient to extend Indefinitely the Life Span of Human Epithelial Stem Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1630.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:The proliferative compartment of stratified epithelia consists of stem and transient amplifying (TA) keratinocytes, which, in the corneal epithelium, are segregated in the limbus and in the central cornea, respectively. In culture replicative senescence occurs when limbal stem cells have generated telomerase-negative TA cells and is mediated by p16ink4a. We show here that enforced telomerase is sufficient to extend indefinitely the life span of human epithelial stem cells in the presence of functional p16ink4a. Methods:hTERT transduced keratinocytes respond to growth inhibitory and differentiation stimuli and, upon DNA damage, halt cell division by activating p53. Results: Telomerase induces bypass of senescence in limbal but not corneal keratinocytes. this suggests that telomerase is sufficient to extend the life span of keratinocyte stem, but not TA, cells and that keratinocytes might reach a point of their replicative history beyond which their proliferative capacity cannot be extended by enforced telomerase only.Conclusion: Our data suggest that telomere-dependent senescence is indeed a general property of human somatic cells, argue against a telomere-independent mechanism for counting cell divisions, and give new insights in epithelial tumorigenesis, in light of the notion that keratinocyte stem cells are thought to be involved in the formation of skin and corneal cancer.
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