Conditional telomerase induction causes proliferation of hair follicle stem cells

被引:341
作者
Sarin, KY
Cheung, P
Gilison, D
Lee, E
Tennen, RI
Wang, E
Artandi, MK
Oro, AE
Artandi, SE [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Med, Div Hematol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Canc Biol Program, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Dept Dermatol, Stanford, CA 94305 USA
关键词
D O I
10.1038/nature03836
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
TERT, the protein component of telomerase(1,2), 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 cells(3), 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.
引用
收藏
页码:1048 / 1052
页数:5
相关论文
共 30 条
[1]   Stem cells in the skin: waste not, Wnt not [J].
Alonso, L ;
Fuchs, E .
GENES & DEVELOPMENT, 2003, 17 (10) :1189-1200
[2]   Constitutive telomerase expression promotes mammary carcinomas in aging mice [J].
Artandi, SE ;
Alson, S ;
Tietze, MK ;
Sharpless, NE ;
Ye, S ;
Greenberg, RA ;
Castrillon, DH ;
Horner, JW ;
Weiler, SR ;
Carrasco, RD ;
DePinho, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (12) :8191-8196
[3]   Switching and signaling at the telomere [J].
Blackburn, EH .
CELL, 2001, 106 (06) :661-673
[4]   Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche [J].
Blanpain, C ;
Lowry, WE ;
Geoghegan, A ;
Polak, L ;
Fuchs, E .
CELL, 2004, 118 (05) :635-648
[5]   Evolving views of telomerase and cancer [J].
Blasco, MA ;
Hahn, WC .
TRENDS IN CELL BIOLOGY, 2003, 13 (06) :289-294
[6]   Telomere shortening and tumor formation by mouse cells lacking telomerase RNA [J].
Blasco, MA ;
Lee, HW ;
Hande, MP ;
Samper, E ;
Lansdorp, PM ;
DePinho, RA ;
Greider, CW .
CELL, 1997, 91 (01) :25-34
[7]   Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis [J].
Braun, KM ;
Niemann, C ;
Jensen, UB ;
Sundberg, JP ;
Silva-Vargas, V ;
Watt, FM .
DEVELOPMENT, 2003, 130 (21) :5241-5255
[8]   Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression [J].
Chang, S ;
Khoo, CM ;
Naylor, ML ;
Maser, RS ;
DePinho, RA .
GENES & DEVELOPMENT, 2003, 17 (01) :88-100
[9]   LABEL-RETAINING CELLS RESIDE IN THE BULGE AREA OF PILOSEBACEOUS UNIT - IMPLICATIONS FOR FOLLICULAR STEM-CELLS, HAIR CYCLE, AND SKIN CARCINOGENESIS [J].
COTSARELIS, G ;
SUN, TT ;
LAVKER, RM .
CELL, 1990, 61 (07) :1329-1337
[10]   Telomerase and differentiation in multicellular organisms: Turn it off, turn it on, and turn it off again [J].
Forsyth, NR ;
Wright, WE ;
Shay, JW .
DIFFERENTIATION, 2002, 69 (4-5) :188-197