Mechanisms of Development, ( ISI ), Year (2005-9)

Title : The CDK inhibitor p27enhances neural differentiation in pluripotent NTERA2 human EC cells, but does ( The CDK inhibitor p27enhances neural differentiation in pluripotent NTERA2 human EC cells, but does )

Authors: Ahmad Reza Bahrami , Maryam Moghaddam Matin , Peter W. Andrews ,

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Embryonal carcinoma (EC) cells, the stem cells of teratocarcinomas, are the malignant counterparts of pluripotent embryonic stem (ES) cells, but commonly exhibit a reduced ability to differentiate, presumably because of continual selection for genetic changes that alter the balance between self-renewal, differentiation and apoptosis in favour of self-renewal. To explore the nature of the genetic changes that promote nullipotency, we have compared two human EC cell lines, a ‘nullipotent’ line, 2102Ep, and a ‘pluripotent’ line, NTERA2. A hybrid derived by fusion of these cells differentiates in response to retinoic acid but, unlike the parental NTERA2 line, does not form terminally differentiated neurons. This implies that the nullipotent EC cell line, 2102Ep, differs in expression of at least two functions in comparison with the NTERA2 pluripotent line, one affecting commitment to differentiation, and one affecting terminal neural differentiation. We have now investigated the possible role of the CDK inhibitor, p27kip1 (p27) in commitment and terminal differentiation. In NTERA2, but not in 2102Ep cells, retinoic acid induces up-regulation of p27 expression, suggesting that 2102Ep cells lack this capacity. However, constitutive expression of a p27 transgene does not overcome the block to differentiation in the 2102Ep parental cells; commitment to differentiation must be blocked elsewhere. On the other hand, constitutive over-expression of p27 from a transgene enhances the neural differentiation of NTERA2 cells. Our results suggest that p27 plays a role in terminal neuronal differentiation of human EC cells, but not in their initial commitment to differentiation, and that other factors, possibly Cyclin D2, specifically limit its ability to promote neural differentiation.

Keywords

Embryonal carcinoma; Germ cell tumours;
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@article{paperid:202970,
author = {Bahrami, Ahmad Reza and Moghaddam Matin, Maryam and Peter W. Andrews},
title = {The CDK inhibitor p27enhances neural differentiation in pluripotent NTERA2 human EC cells, but does},
journal = {Mechanisms of Development},
year = {2005},
month = {September},
issn = {0925-4773},
keywords = {Embryonal carcinoma; Germ cell tumours; Pluripotent},
}

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%0 Journal Article
%T The CDK inhibitor p27enhances neural differentiation in pluripotent NTERA2 human EC cells, but does
%A Bahrami, Ahmad Reza
%A Moghaddam Matin, Maryam
%A Peter W. Andrews
%J Mechanisms of Development
%@ 0925-4773
%D 2005

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