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First published online 1 February 2005
doi: 10.1242/jcs.01673

Journal of Cell Science 118, 819-829 (2005)
Published by The Company of Biologists 2005
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Research Article

Ectopic mTERT expression in mouse embryonic stem cells does not affect differentiation but confers resistance to differentiation- and stress-induced p53-dependent apoptosis

Ming Kei Lee1, M. Prakash Hande2,3 and Kanaga Sabapathy1,4,*

1 National Cancer Centre, 11, Hospital Drive, Singapore 169610, Republic of Singapore
2 Oncology Research Institute, NUMI, National University of Singapore, Singapore 117597, Republic of Singapore
3 Department of Physiology, National University of Singapore, 8, Medical Drive, Singapore 117597, Republic of Singapore
4 Department of Biochemistry, National University of Singapore, 8, Medical Drive, Singapore 117597, Republic of Singapore

* Author for correspondence (e-mail: cmrksb{at}nccs.com.sg)

Accepted 2 December 2004

The fundamental role of telomerase is to protect telomere ends and to maintain telomere length during replication; hence, telomerase expression is high in stem cells but reduced upon differentiation. Recent studies indicate that telomerase might play other roles besides telomere maintenance. We have investigated the role of telomerase in cellular differentiation and death. Here, we show that ectopic expression of mouse telomerase catalytic subunit (mTERT) does not affect embryonic stem (ES) cell proliferation or differentiation in vitro, but protects ES cells against cell death during differentiation. Ectopic mTERT expression also confers resistance to apoptosis induced by oxidative stress and other genotoxic insults. This resistance depends on the catalytic activity of mTERT. Stress-signal-induced p53 accumulation and consequent p53-dependent apoptotic target gene expression was not affected by mTERT overexpression. However, although chemical inhibition of p53 by {alpha}-pifithrin reduced stress-induced apoptosis in vector-expressing cells, it did not significantly affect apoptosis in mTERT-expressing cells. Moreover, overexpression of mTERT in p53–/– ES cells did not confer further resistance to genotoxic insults, suggesting that mTERT might exert its protective effect by antagonizing the p53 pathway. Altogether, our findings indicate that ectopic mTERT expression in ES cells does not affect differentiation but confers resistance to apoptosis, and suggest that this strategy might be used in improving the efficiency of stem-cell therapies.

Key words: Apoptosis, Differentiation, ES cells, mTERT, p53, Stress signals


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