Conditional Telomerase Induction Causes Proliferation of Hair Follicle Stem Cells

Nature. 2005 Aug 18;436(7053):1048-52. doi: 10.1038/nature03836.

Abstract

TERT, the protein component of telomerase, 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 cells, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Enzyme Induction
  • Hair Follicle / cytology*
  • Hair Follicle / enzymology
  • Mice
  • Mice, Transgenic
  • RNA / genetics
  • Stem Cells / cytology*
  • Stem Cells / enzymology
  • Telomerase / deficiency
  • Telomerase / genetics*
  • Telomerase / metabolism*
  • Transgenes / genetics

Substances

  • DNA-Binding Proteins
  • telomerase RNA
  • RNA
  • TERT protein, human
  • Telomerase
  • Tert protein, mouse
  • Bromodeoxyuridine