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First published online March 20, 2009

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Activin and Nanog: a pluripotent mix

Pluripotency, the ability to give rise to all the cell lineages of the body, is a hallmark of embryonic stem cells (ESCs), and understanding its regulation is essential for effectively controlling ESC differentiation. Ludovic Vallier, Roger Pedersen and colleagues now demonstrate a role for Nanog - a crucial component of the pluripotency transcriptional network - in safeguarding human ESCs (hESCs) against the differentiation-inducing effects of extracellular signals (p. 1339). They show that Activin/Nodal signalling, which maintains hESC pluripotency through SMAD2/3 activation, maintains NANOG expression through the binding of SMAD2/3 to the NANOG promoter, which blocks the differentiation of pluripotent cells into neuroectoderm. Conversely, NANOG appears to limit the Activin/Nodal-induced transcriptional activity of SMAD2/3 by forming a protein complex with it. This interaction prevents the differentiation of pluripotent cells from mesendoderm into endoderm, which is otherwise induced by exposure to BMP4 and Activin/Nodal signalling. From their findings, the researchers propose that a negative-feedback loop involving Nanog and Smad2/3 safeguards pluripotent cells against differentiation.

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Activin/Nodal signalling maintains pluripotency by controlling Nanog expression

Ludovic Vallier, Sasha Mendjan, Stephanie Brown, Zhenzhi Chng, Adrian Teo, Lucy E. Smithers, Matthew W. B. Trotter, Candy H.-H. Cho, Amelie Martinez, Peter Rugg-Gunn, Gabrielle Brons, and Roger A. Pedersen
Development 2009 136: 1339-1349. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?