Conditional telomerase induction causes proliferation of hair follicle stem cells

Abstract

Regenerating tissues such as skin and blood require high rates of cell turnover, which occurs through the tightly regulated division of tissue stem cells. The genes and proteins that control stem-cell behaviour remain largely unknown, but now a critical connection between stem-cell function and the protein component of telomerase, TERT, has been discovered. Conditional activation of TERT in skin epithelium activates resting hair follicle stem cells, resulting in rapid hair growth. This is distinct from TERT's role in extending telomeres, the caps that protect the ends of chromosomes, and suggests new ways of treating disorders associated with tissue injury and ageing. TERT, the protein component of telomerase1,2, serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends, and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells3, but its role in these compartments is not fully understood. Here we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen (the resting phase of the hair follicle cycle) to anagen (the active phase), thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region. This new function for TERT does not require the telomerase RNA component, which encodes the template for telomere addition, and therefore operates through a mechanism independent of its activity in synthesizing telomere repeats. These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway.