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Effects of Telomerase and Telomere Length on Epidermal Stem Cell Behavior
Ignacio Flores,María L. Cayuela,María A. Blasco*
A key process in organ homeostasis is the mobilization of stemcells out of their niches. We show through analysis of mousemodels that telomere length, as well as the catalytic componentof telomerase, Tert, are critical determinants in the mobilizationof epidermal stem cells. Telomere shortening inhibited mobilizationof stem cells out of their niche, impaired hair growth, andresulted in suppression of stem cell proliferative capacityin vitro. In contrast, Tert overexpression in the absence ofchanges in telomere length promoted stem cell mobilization,hair growth, and stem cell proliferation in vitro. The effectsof telomeres and telomerase on stem cell biology anticipatetheir role in cancer and aging.
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid E-28029, Spain.
* To whom correspondence should be addressed. E-mail: mblasco{at}cnio.es
Telomere Shortening in Neural Stem Cells Disrupts Neuronal Differentiation and Neuritogenesis.
S. R. Ferron, M. A. Marques-Torrejon, H. Mira, I. Flores, K. Taylor, M. A. Blasco, and I. Farinas (2009)
J. Neurosci.
29, 14394-14407
|Abstract »|Full Text »|PDF »
Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase.
Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice.
P. Martinez, M. Thanasoula, P. Munoz, C. Liao, A. Tejera, C. McNees, J. M. Flores, O. Fernandez-Capetillo, M. Tarsounas, and M. A. Blasco (2009)
Genes & Dev.
23, 2060-2075
|Abstract »|Full Text »|PDF »
Activation of Telomerase by Human Cytomegalovirus.
K. Straat, C. Liu, A. Rahbar, Q. Zhu, L. Liu, N. Wolmer-Solberg, F. Lou, Z. Liu, J. Shen, J. Jia, et al. (2009)
J Natl Cancer Inst
101, 488-497
|Abstract »|Full Text »|PDF »
TRF1 Controls Telomere Length and Mitotic Fidelity in Epithelial Homeostasis.
P. Munoz, R. Blanco, G. de Carcer, S. Schoeftner, R. Benetti, J. M. Flores, M. Malumbres, and M. A. Blasco (2009)
Mol. Cell. Biol.
29, 1608-1625
|Abstract »|Full Text »|PDF »
Genetic dissection of the mechanisms underlying telomere-associated diseases: impact of the TRF2 telomeric protein on mouse epidermal stem cells.
REVIEW PAPER: Origin and Molecular Pathology of Adrenocortical Neoplasms.
M. Bielinska, H. Parviainen, S. Kiiveri, M. Heikinheimo, and D. B. Wilson (2009)
Vet. Pathol.
46, 194-210
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Telomere biology in cardiovascular disease: the TERC-/- mouse as a model for heart failure and ageing.
L. S.M. Wong, H. Oeseburg, R. A. de Boer, W. H. van Gilst, D. J. van Veldhuisen, and P. van der Harst (2009)
Cardiovasc Res
81, 244-252
|Abstract »|Full Text »|PDF »
Lung alveolar integrity is compromised by telomere shortening in telomerase-null mice.
J. Lee, R. Reddy, L. Barsky, J. Scholes, H. Chen, W. Shi, and B. Driscoll (2009)
Am J Physiol Lung Cell Mol Physiol
296, L57-L70
|Abstract »|Full Text »|PDF »
Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells.
D. T. Breault, I. M. Min, D. L. Carlone, L. G. Farilla, D. M. Ambruzs, D. E. Henderson, S. Algra, R. K. Montgomery, A. J. Wagers, and N. Hole (2008)
PNAS
105, 10420-10425
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Therapeutic Implications of Leukemic Stem Cell Pathways.
S. Chumsri, W. Matsui, and A. M Burger (2008)
Am. Assoc. Cancer Res. Educ. Book
2008, 397-406
|Abstract »|Full Text »|PDF »
Nuclear envelope defects cause stem cell dysfunction in premature-aging mice.
J. Espada, I. Varela, I. Flores, A. P. Ugalde, J. Cadinanos, A. M. Pendas, C. L. Stewart, K. Tryggvason, M. A. Blasco, J. M.P. Freije, et al. (2008)
J. Cell Biol.
181, 27-35
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The longest telomeres: a general signature of adult stem cell compartments.
I. Flores, A. Canela, E. Vera, A. Tejera, G. Cotsarelis, and M. A. Blasco (2008)
Genes & Dev.
22, 654-667
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Telomerase reverse transcriptase expression elevated by avian leukosis virus integration in B cell lymphomas.
F. Yang, R. R. Xian, Y. Li, T. S. Polony, and K. L. Beemon (2007)
PNAS
104, 18952-18957
|Abstract »|Full Text »|PDF »
Therapeutic Implications of Leukemic Stem Cell Pathways.
S. Chumsri, W. Matsui, and A. M. Burger (2007)
Clin. Cancer Res.
13, 6549-6554
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Reply.
I. Spyridopoulos, C. K. Kissel, S. Dimmeler, and A. M. Zeiher (2007)
J. Am. Coll. Cardiol.
50, 1912-1913
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Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow).
A. P. Beltrami, D. Cesselli, N. Bergamin, P. Marcon, S. Rigo, E. Puppato, F. D'Aurizio, R. Verardo, S. Piazza, A. Pignatelli, et al. (2007)
Blood
110, 3438-3446
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Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres.
I. Siegl-Cachedenier, I. Flores, P. Klatt, and M. A. Blasco (2007)
J. Cell Biol.
179, 277-290
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Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals.
N. Ohtani, Y. Imamura, K. Yamakoshi, F. Hirota, R. Nakayama, Y. Kubo, N. Ishimaru, A. Takahashi, A. Hirao, T. Shimizu, et al. (2007)
PNAS
104, 15034-15039
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Regulation and Effects of Modulation of Telomerase Reverse Transcriptase Expression in Primordial Germ Cells During Development.
M. Coussens, Y. Yamazaki, S. Moisyadi, R. Suganuma, R. Yanagimachi, and R. Allsopp (2006)
Biol Reprod
75, 785-791
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Transforming Growth Factor beta Suppresses Human Telomerase Reverse Transcriptase (hTERT) by Smad3 Interactions with c-Myc and the hTERT Gene.
H. Li, D. Xu, J. Li, M. C. Berndt, and J.-P. Liu (2006)
J. Biol. Chem.
281, 25588-25600
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Genetic analysis of myc and telomerase interactions in vivo..
I. Flores, G. Evan, and M. A. Blasco (2006)
Mol. Cell. Biol.
26, 6130-6138
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Assembly of Mutant-Template Telomerase RNA into Catalytically Active Telomerase Ribonucleoprotein That Can Act on Telomeres Is Required for Apoptosis and Cell Cycle Arrest in Human Cancer Cells.