Open AccessA competitive protein interaction network buffers Oct4‐mediated differentiation to promote pluripotency in embryonic stem cells
Author(s) -
Muñoz Descalzo Silvia,
Rué Pau,
Faunes Fernando,
Hayward Penelope,
Jakt Lars Martin,
Balayo Tina,
GarciaOjalvo Jordi,
Martinez Arias Alfonso
Publication year - 2013
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2013.49
Subject(s) - homeobox protein nanog , biology , embryonic stem cell , nanog homeobox protein , microbiology and biotechnology , rex1 , cell potency , induced pluripotent stem cell , stem cell , cellular differentiation , transcription factor , gene regulatory network , function (biology) , regulation of gene expression , genetics , gene expression , gene
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.