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 language | English |
---|---|
Article number | 694 |
Journal | Molecular Systems Biology |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2013 |
Keywords
- Oct4
- mathematical modelling
- pluripotency
- protein network
- β-catenin
ASJC Scopus subject areas
- Information Systems
- General Immunology and Microbiology
- Applied Mathematics
- General Biochemistry,Genetics and Molecular Biology
- General Agricultural and Biological Sciences
- Computational Theory and Mathematics