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Sokolik C, Liu Y, Bauer D, et al. Transcription factor competition allows embryonic stem cells to distinguish authentic signals from noise. Cell Syst. 2015;1(2):117-129doi: 10.1016/j.cels.2015.08.001.
Sokolik, C., Liu, Y., Bauer, D., McPherson, J., Broeker, M., Heimberg, G., Qi, L. S., Sivak, D. A., & Thomson, M. (2015). Transcription factor competition allows embryonic stem cells to distinguish authentic signals from noise. Cell systems, 1(2), 117-129. https://doi.org/10.1016/j.cels.2015.08.001
Sokolik, Cameron, et al. "Transcription factor competition allows embryonic stem cells to distinguish authentic signals from noise." Cell systems vol. 1,2 (2015): 117-129. doi: https://doi.org/10.1016/j.cels.2015.08.001
Sokolik C, Liu Y, Bauer D, McPherson J, Broeker M, Heimberg G, Qi LS, Sivak DA, Thomson M. Transcription factor competition allows embryonic stem cells to distinguish authentic signals from noise. Cell Syst. 2015 Aug 26;1(2):117-129. doi: 10.1016/j.cels.2015.08.001. PMID: 26405695; PMCID: PMC4576702.
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Cell Syst. 2015 Aug 26;1(2):117-129. doi: 10.1016/j.cels.2015.08.001.

Transcription factor competition allows embryonic stem cells to distinguish authentic signals from noise.

Cell systems

Cameron Sokolik, Yanxia Liu, David Bauer, Jade McPherson, Michael Broeker, Graham Heimberg, Lei S Qi, David A Sivak, Matt Thomson

Affiliations

  1. Center for Systems and Synthetic Biology, University of California, San Francisco; San Francisco, California, 94158. USA ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco; San Francisco, California, 94158. USA.
  2. Center for Systems and Synthetic Biology, University of California, San Francisco; San Francisco, California, 94158. USA.

PMID: 26405695 PMCID: PMC4576702 DOI: 10.1016/j.cels.2015.08.001

Abstract

Stem cells occupy variable environments where they must distinguish stochastic fluctuations from developmental cues. Here, we use optogenetics to investigate how the pluripotency network in embryonic stem (ES) cells achieves a robust response to differentiation cues but not to gene expression fluctuations. We engineered ES cells in which we could quantitatively ontrol the endogenous mechanism of neural differentiation through a light-inducible Brn2 transgene and monitor differentiation status through a genome-integrated Nanog-GFP reporter. By exposing cells to pulses of Brn2, we find that the pluripotency network rejects Brn2 inputs that are below specific magnitude or duration thresholds, but allows rapid differentiation when both thresholds are satisfied. The filtering properties of the network arise through its positive feedback architecture and the intrinsic half-life of Nanog, which determines the duration threshold in the network. Together our results suggest that the dynamic properties of positive-feedback networks might determine how inputs are classified as signal or noise by stem cells.

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