@article{TEXTUAL,
      recid = {9891},
      author = {Kellogg, Ryan A. and Tian, Chengzhe and Lipniacki, Tomasz  and Quake, Stephen R. and Tay, Savaş},
      title = {Digital signaling decouples activation probability and  population heterogeneity},
      journal = {eLife},
      address = {2015-10-21},
      number = {TEXTUAL},
      abstract = {Digital signaling enhances robustness of cellular  decisions in noisy environments, but it is unclear how  digital systems transmit temporal information about a  stimulus. To understand how temporal input information is  encoded and decoded by the NF-κB system, we studied  transcription factor dynamics and gene regulation under  dose- and duration-modulated inflammatory inputs.  Mathematical modeling predicted and microfluidic  single-cell experiments confirmed that integral of the  stimulus (or area, concentration × duration) controls the  fraction of cells that activate NF-κB in the population.  However, stimulus temporal profile determined NF-κB  dynamics, cell-to-cell variability, and gene expression  phenotype. A sustained, weak stimulation lead to  heterogeneous activation and delayed timing that is  transmitted to gene expression. In contrast, a transient,  strong stimulus with the same area caused rapid and uniform  dynamics. These results show that digital NF-κB signaling  enables multidimensional control of cellular phenotype via  input profile, allowing parallel and independent control of  single-cell activation probability and population  heterogeneity.},
      url = {http://knowledge.uchicago.edu/record/9891},
}