Journal article
Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Nature (London), Vol.464(7286), pp.292-296
03/11/2010
DOI: 10.1038/nature08792
PMCID: PMC3058620
PMID: 20164838
Abstract
Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues
1
–
3
. Patient-specific induced pluripotent stem (iPS) cells
4
represent invaluable
in vitro
models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of telomerase reverse transcriptase (
TERT
)
5
–
7
. We investigated whether defects in telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in telomerase RNA component (
TERC
) levels to restore telomere maintenance and self-renewal. We discovered that
TERC
upregulation is a feature of the pluripotent state, that multiple telomerase components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3' deletion at the
TERC
locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting telomerase, and suggest that strategies to increase
TERC
expression may be therapeutically beneficial in DC patients.
Details
- Title: Subtitle
- Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
- Creators
- Suneet Agarwal - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAYuin-Han Loh - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAErin M McLoughlin - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAJunjiu Huang - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAIn-Hyun Park - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAJustine D Miller - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAHongguang Huo - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAMaja Okuka - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USARosana Maria dos Reis - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USASabine Loewer - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAHuck-Hui Ng - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USADavid L Keefe - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAFrederick D Goldman - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAAloysius J Klingelhutz - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USALin Liu - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USAGeorge Q Daley - Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA USA
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.464(7286), pp.292-296
- DOI
- 10.1038/nature08792
- PMID
- 20164838
- PMCID
- PMC3058620
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 03/11/2010
- Academic Unit
- Microbiology and Immunology; Radiation Oncology
- Record Identifier
- 9984001132602771
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