A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in embryonic stem cells
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- dc.contributor.author Muñoz Descalzo, Silviaca
- dc.contributor.author Rué, Pauca
- dc.contributor.author Faunes, Fernandoca
- dc.contributor.author Hayward, Penelopeca
- dc.contributor.author Jakt, Lars Martinca
- dc.contributor.author Balayo, Tinaca
- dc.contributor.author García Ojalvo, Jordica
- dc.contributor.author Martínez Arias, Alfonsoca
- dc.date.accessioned 2015-12-01T18:48:36Z
- dc.date.available 2015-12-01T18:48:36Z
- dc.date.issued 2013
- dc.description.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.ca
- dc.format.mimetype application/pdfca
- dc.identifier.citation Muñoz Descalzo S, Rué P, Faunes F, Hayward P, Jakt LM, Balayo T et al. A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in embryonic stem cells. Molecular systems biology. 2013;9:694. DOI: 10.1038/msb.2013.49ca
- dc.identifier.doi http://dx.doi.org/10.1038/msb.2013.49
- dc.identifier.issn 1744-4292
- dc.identifier.uri http://hdl.handle.net/10230/25292
- dc.language.iso engca
- dc.publisher Nature Publishing Groupca
- dc.relation.ispartof Molecular systems biology. 2013;9:694
- dc.rights © Nature Publishing Group. http://10.1038/msb.2013.49. This work is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/3.0/ca
- dc.subject.other Cèl·lules mareca
- dc.subject.other Ratolins (Animals de laboratori) -- Embriologiaca
- dc.title A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in embryonic stem cellsca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca