Aside from telomere maintenance telomerase reverse transcriptase appears to be also involved in stem cell mobilization suggesting that pertubations of its expression in normal tissues could have unforeseen consequences.
Effects of Telomerase and Telomere Length on Epidermal Stem Cell Behavior.
Flores I, Cayuela ML, Blasco MA.
Science. 2005 Jul 21
A key process in organ homeostasis is the mobilization of stem cells out of their niches. We show through analysis of mouse models that telomere length, as well as the catalytic component of telomerase, Tert, are critical determinants in the mobilization of epidermal stem cells. Telomere shortening inhibited mobilization of stem cells out of their niche, impaired hair growth, and resulted in suppression of stem cell proliferative capacity in vitro. In contrast, Tert overexpression in the absence of changes in telomere length promoted stem cell mobilization, hair growth, and stem cell proliferation in vitro. The effects of telomeres and telomerase on stem cell biology anticipate their role in cancer and aging.
Nature Reviews Molecular Cell Biology, published online 15 August 2005
More than just the 'maintenance man'
Shannon Amoils
In higher organisms, the proliferative and multipotent properties of adult stem cells enable the maintenance and regeneration of different tissues. These stem cells express high levels of telomerase, which is the ribonucleoprotein enzyme that extends telomeres during DNA duplication. As telomeres must be sufficiently long for cell division to take place, the increased activity of telomerase is probably one of the factors that endow these cells with their large proliferative capacity.
But does telomerase have other roles in the stem-cell compartment apart from the maintenance of chromosome ends? A group of scientists led by Maria Blasco at the Spanish National Cancer Center tackled this question by analysing the behaviour of epidermal stem cells in mouse models of defective telomerase expression.
The authors showed that, in G1 telomerase deficient (Terc-/-) mice, in which telomeres are only slightly reduced in length, and in G3 Terc-/- mice, which have critically short telomeres, epidermal stem cells accumulated in their niche in the bulge of the hair follicle. Cells from both G1 and G3 mice were unable to mobilize efficiently from the bulge and did not initiate appropriate hair growth in response to a proliferative stimulus. Also, the in vitro proliferative capacity of epidermal stem cells derived from both G1 and G3 Terc-/- mice was impaired.
By contrast, in K5-mTert mice, in which epidermal stem cells overexpress the protein component of telomerase, the hair follicle niche was depleted of stem cells and, compared to wild-type mice, an increased proportion of these cells was mobilized by a proliferative stimulus. These cells also showed a markedly increased capacity to proliferate in vitro.
Taken together, these results indicate that the role of telomerase is not merely to maintain chromosome ends — telomerase activity per se has a crucial role in regulating stem-cell turnover and mobilization. As Terc-/- mice have an ageing-resistant phenotype, and K5-mTert mice have a propensity to develop skin tumours, these effects of telomerase on stem-cell behaviour are crucial in the aetiology of both cancer and ageing.