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Title: A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in embryonic stem cells
Authors: Muñoz Descalzo, Silvia 
Rué, Pau
Faunes, Fernando
Hayward, Penelope
Jakt, Lars Martin
Balayo, Tina
Garcia-Ojalvo, Jordi
Martinez Arias, Alfonso
UNESCO Clasification: 32 Ciencias médicas
2415 Biología molecular
Keywords: b-catenin
Mathematical modelling
Protein network
Issue Date: 2013
Journal: Molecular Systems Biology 
Abstract: Pluripotency in embryonic stem cells is maintained through the activity of a small set of transcription factors centred around Oct4 and Nanog, which control the expression of 'self-renewal' and 'differentiation' genes. Here, we combine single-cell quantitative immunofluorescence microscopy and gene expression analysis, together with theoretical modelling, to investigate how the activity of those factors is regulated. We uncover a key role for post-translational regulation in the maintenance of pluripotency, which complements the well-established transcriptional regulatory layer. Specifically, we find that the activity of a network of protein complexes involving Nanog, Oct4, Tcf3, and β-catenin suffices to account for the behavior of ES cells under different conditions. Our results suggest that the function of the network is to buffer the transcriptional activity of Oct4, which appears to be the main determinant to exit pluripotency. The protein network explains the mechanisms underlying the gain and loss of function in different mutants, and brings us closer to a full understanding of the molecular basis of pluripotency.
ISSN: 1744-4292
DOI: 10.1038/msb.2013.49
Source: Molecular Systems Biology [1744-4292],v. 9 (694) (Octubre 2013)
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