A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in embryonic stem cells

Silvia Muñoz Descalzo, Pau Rué, Fernando Faunes, Penelope Hayward, Lars Martin Jakt, Tina Balayo, Jordi Garcia-Ojalvo, Alfonso Martinez Arias

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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.

Original languageEnglish
Article number694
JournalMolecular Systems Biology
Volume9
Issue number1
DOIs
Publication statusPublished - 2013

Keywords

  • Oct4
  • mathematical modelling
  • pluripotency
  • protein network
  • β-catenin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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