Molecular Biology of the Cell Sign up for new MBC in Press e-TOCs!

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print February 6, 2008
Mol. Biol. Cell 10.1091/mbc.E06-11-1013

A more recent version of this article appeared on April 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E06-11-1013v1
19/4/1548    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schwob, A. E.
Right arrow Articles by Meiri, K. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schwob, A. E.
Right arrow Articles by Meiri, K. F.

Submitted on November 15, 2006
Revised on January 3, 2008
Accepted on January 28, 2008

Immortalization of Neural Precursors when Telomerase is Overexpressed in Embryonal Carcinomas and Stem Cells

Anneke E. Schwob,* Lilly J. Nguyen,* and Karina F. Meiri

Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston MA 02111, USA

Monitoring Editor: Marianne Bronner-Fraser

The DNA repair enzyme telomerase maintains chromosome stability by ensuring that telomeres regenerate each time the cell divides, protecting chromosome ends. During onset of neuroectodermal differentiation in P19 embryonal carcinoma (EC) cells three independent techniques (Southern blotting, Q-FISH and Q-PCR) revealed a catastrophic reduction in telomere length in nestin-expressing neuronal precursors even though telomerase activity remained high. Overexpressing telomerase protein (mTERT) prevented telomere collapse and the neuroepithelial precursors produced continued to divide, but deaggregated and died. Addition of FGF-2 prevented deaggregation, protected the precursors from the apoptotic event that normally accompanies onset of terminal neuronal differentiation, allowed them to evade senescence, and enabled completion of morphological differentiation. Similarly, primary embryonic stem (ES) cells overexpressing mTERT also initiated neuroectodermal differentiation efficiently, acquiring markers of neuronal precursors and mature neurons. ES precursors are normally cultured with FGF-2, and overexpression of mTERT alone was sufficient to allow them to evade senescence. However, when FGF-2 was removed in order for differentiation to be completed most neural precursors underwent apoptosis indicating that in ES cells mTERT is not sufficient allow terminal differentiation of ES neural precursors in vitro. The results demonstrate that telomerase can potentiate the transition between pluripotent stem cell and committed neuron in both EC and ES cells.

*These authors contributed equally to this work.

Address correspondence to: Karina F. Meiri (karina.meiri{at}tufts.edu)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.