DOI: 10.1038/msb.2013.49. A competitive protein interaction network buffers Oct4‐mediated differentiation to promote pluripotency in embryonic stem cells

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

10.1038/msb.2013.49

Crossref journal-article

Springer Science and Business Media LLC

Molecular Systems Biology (297)

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.

Bibliography

MuÃ±oz Descalzo, S., RuÃ©, P., Faunes, F., Hayward, P., Jakt, L. M., Balayo, T., GarciaâOjalvo, J., & Martinez Arias, A. (2013). A competitive protein interaction network buffers Oct4âmediated differentiation to promote pluripotency in embryonic stem cells. Molecular Systems Biology, 9(1). Portico.

Authors 8

Silvia Muñoz Descalzo (first)
Pau Rué (additional)
Fernando Faunes (additional)
Penelope Hayward (additional)
Lars Martin Jakt (additional)
Tina Balayo (additional)
Jordi Garcia‐Ojalvo (additional)
Alfonso Martinez Arias (additional)

References 53 Referenced 40

Dates

Type	When
Created	11 years, 10 months ago (Oct. 8, 2013, 10:01 a.m.)
Deposited	1 year, 8 months ago (Dec. 18, 2023, 3:54 p.m.)
Indexed	1 month, 1 week ago (July 30, 2025, 6:35 a.m.)
Issued	12 years, 8 months ago (Jan. 1, 2013)
Published	12 years, 8 months ago (Jan. 1, 2013)
Published Online	11 years, 10 months ago (Oct. 8, 2013)
Published Print	12 years, 8 months ago (Jan. 1, 2013)

Funders 0

None

BibTeX

@article{Mu_oz_Descalzo_2013, title={A competitive protein interaction network buffers Oct4‐mediated differentiation to promote pluripotency in embryonic stem cells}, volume={9}, ISSN={1744-4292}, url={http://dx.doi.org/10.1038/msb.2013.49}, DOI={10.1038/msb.2013.49}, number={1}, journal={Molecular Systems Biology}, publisher={Springer Science and Business Media LLC}, author={Muñoz Descalzo, Silvia and Rué, Pau and Faunes, Fernando and Hayward, Penelope and Jakt, Lars Martin and Balayo, Tina and Garcia‐Ojalvo, Jordi and Martinez Arias, Alfonso}, year={2013}, month=jan }

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