| Title | A Noisy Paracrine Signal Determines the Cellular NF-{kappa}B Response to Lipopolysaccharide. | | Author(s) | Lee TK, Denny EM, Sanghvi JC, Gaston JE, Maynard ND, Hughey JJ, Covert MW | | Institution | 1Bioengineering Department, Stanford University, 318 Campus Drive West, Stanford, CA 94305-5444, USA. | | Source | Sci Signal 2009; 2(93):ra65. | | Abstract | Nearly identical cells can exhibit substantially different responses to the same stimulus. We monitored the nuclear localization dynamics of nuclear factor kappaB (NF-kappaB) in single cells stimulated with tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS). Cells stimulated with TNF-alpha have quantitative differences in NF-kappaB nuclear localization, whereas LPS-stimulated cells can be clustered into transient or persistent responders, representing two qualitatively different groups based on the NF-kappaB response. These distinct behaviors can be linked to a secondary paracrine signal secreted at low concentrations, such that not all cells undergo a second round of NF-kappaB activation. From our single-cell data, we built a computational model that captures cell variability, as well as population behaviors. Our findings show that mammalian cells can create "noisy" environments to produce diversified responses to stimuli. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19843957 |
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