Format

Send to

Choose Destination
Nat Cell Biol. 2015 Oct;17(10):1235-46. doi: 10.1038/ncb3237. Epub 2015 Sep 21.

Network plasticity of pluripotency transcription factors in embryonic stem cells.

Author information

1
Research Unit Stem Cell Dynamics, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
2
Institute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
3
Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
4
Technische Universität München, Center for Mathematics, Chair of Mathematical Modelling of Biological Systems, Boltzmannstraße 3, 85748 Garching, Germany.
5
Stem Cell Engineering, Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany.

Abstract

Transcription factor (TF) networks are thought to regulate embryonic stem cell (ESC) pluripotency. However, TF expression dynamics and regulatory mechanisms are poorly understood. We use reporter mouse ESC lines allowing non-invasive quantification of Nanog or Oct4 protein levels and continuous long-term single-cell tracking and quantification over many generations to reveal diverse TF protein expression dynamics. For cells with low Nanog expression, we identified two distinct colony types: one re-expressed Nanog in a mosaic pattern, and the other did not re-express Nanog over many generations. Although both expressed pluripotency markers, they exhibited differences in their TF protein correlation networks and differentiation propensities. Sister cell analysis revealed that differences in Nanog levels are not necessarily accompanied by differences in the expression of other pluripotency factors. Thus, regulatory interactions of pluripotency TFs are less stringently implemented in individual self-renewing ESCs than assumed at present.

PMID:
26389663
DOI:
10.1038/ncb3237
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center