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.