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PMID: 18208333 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.

PLoS genetics ·Vol. 4 ·No. 1 ·2008-01-00 ·Pages e10

Choi J, Southworth LK, Sarin KY, Venteicher AS, Ma W, Chang W, Cheung P, Jun S, Artandi MK, Shah N, Kim SK, Artandi SE

Abstract

Telomerase serves a critical role in stem cell function and tissue homeostasis. This role depends on its ability to synthesize telomere repeats in a manner dependent on the reverse transcriptase (RT) function of its protein component telomerase RT (TERT), as well as on a novel pathway whose mechanism is poorly understood. Here, we use a TERT mutant lacking RT function (TERT(ci)) to study the mechanism of TERT action in mammalian skin, an ideal tissue for studying progenitor cell biology. We show that TERT(ci) retains the full activities of wild-type TERT in enhancing keratinocyte proliferation in skin and in activating resting hair follicle stem cells, which triggers initiation of a new hair follicle growth phase and promotes hair synthesis. To understand the nature of this RT-independent function for TERT, we studied the genome-wide transcriptional response to acute changes in TERT levels in mouse skin. We find that TERT facilitates activation of progenitor cells in the skin and hair follicle by triggering a rapid change in gene expression that significantly overlaps the program controlling natural hair follicle cycling in wild-type mice. Statistical comparisons to other microarray gene sets using pattern-matching algorithms revealed that the TERT transcriptional response strongly resembles those mediated by Myc and Wnt, two proteins intimately associated with stem cell function and cancer. These data show that TERT controls tissue progenitor cells via transcriptional regulation of a developmental program converging on the Myc and Wnt pathways.

MeSH Terms
Algorithms Animals Biopsy Cell Proliferation Dermatologic Surgical Procedures Epithelial Cells/physiology Gene Expression Profiling Gene Expression Regulation, Developmental Hair/metabolism Hair Follicle/cytology,metabolism Immunohistochemistry Keratinocytes/physiology Mice Mice, Transgenic Models, Biological Mutation Proto-Oncogene Proteins c-myc/genetics RNA, Messenger/metabolism Skin/cytology,enzymology,metabolism Stem Cells/cytology,metabolism Telomerase/genetics,metabolism Transcription, Genetic Wnt Proteins/genetics
Chemicals
Proto-Oncogene Proteins c-myc RNA, Messenger Wnt Proteins Telomerase Tert protein, mouse
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Choi Jinkuk
Department of Medicine, Stanford School of Medicine, Stanford, California, United States of America.
Southworth Lucinda K
Sarin Kavita Y
Venteicher Andrew S
Ma Wenxiu
Chang Woody
Cheung Peggie
Jun Sohee
Artandi Maja K
Shah Naman
Kim Stuart K
Artandi Steven E
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.0040010
Published
2008-01-00
Epub
2007-00-13
Pages
e10
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2211538
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007365 · United States
NCI NIH HHS · P01 CA095616 · United States
NCI NIH HHS · R01 CA111691 · United States
NIGMS NIH HHS · GM07365 · United States
NCI NIH HHS · R01 CA125453 · United States
NCI NIH HHS · CA095616 · United States
NCI NIH HHS · CA125453 · United States
NCI NIH HHS · CA111691 · United States
Databases
GEO
GSE9725
External Links
PubMed source DOI: 10.1371/journal.pgen.0040010 PMC Full Text View journal details
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