Conditional telomerase induction causes proliferation of hair follicle stem cells.
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.
Sarin
Kavita Y
KY
Department of Medicine, Division of Hematology, Stanford School of Medicine, Stanford, California 94305, USA.
Cheung
Peggie
P
Gilison
Daniel
D
Lee
Eunice
E
Tennen
Ruth I
RI
Wang
Estee
E
Artandi
Maja K
MK
Oro
Anthony E
AE
Artandi
Steven E
SE
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D004790:Enzyme Induction; D018859:Hair Follicle / Q000166:cytology* / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D012313:RNA / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology; D019098:Telomerase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse; D001973:Bromodeoxyuridine