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生物谷推荐原文出处： Nature doi:10.1038/nature09145 Single-cell NF-κB dynamics reveal digital activation and analogue information processingSava? Tay1,2,4, Jacob J. Hughey1,4, Timothy K. Lee1, Tomasz Lipniacki3, Stephen R. Quake1,2 Markus W. Covert1 Department of Bioengineering, Stanford University, Stanford, California 94305, USAHoward Hughes Medical Institute, Stanford, California 94305, USAInstitute of Fundamental Technological Research, Warsaw 02-106, Poland Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types1. Cell-to-cell communication is primarily mediated by signalling molecules that form spatiotemporal concentration gradients, requiring cells to respond to a wide range of signal intensities2. Here we use high-throughput microfluidic cell culture3 and fluorescence microscopy, quantitative gene expression analysis and mathematical modelling to investigate how single mammalian cells respond to different concentrations of the signalling molecule tumour-necrosis factor (TNF)-α, and relay information to the gene expression programs by means of the transcription factor nuclear factor (NF)-κB. We measured NF-κB activity in thousands of live cells under TNF-α doses covering four orders of magnitude. We find, in contrast to population-level studies with bulk assays2, that the activation is heterogeneous and is a digital process at the single-cell level with fewer cells responding at lower doses. Cells also encode a subtle set of analogue parameters to modulate the outcome; these parameters include NF-κB peak intensity, response time and number of oscillations. We developed a stochastic mathematical model that reproduces both the digital and analogue dynamics as well as most gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-α-induced NF-κB si