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Sci Signal. 2009 Oct 20;2(93):ra65. doi: 10.1126/scisignal.2000599.

A noisy paracrine signal determines the cellular NF-kappaB response to lipopolysaccharide.

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1
Bioengineering Department, Stanford University, 318 Campus Drive West, Stanford, CA 94305-5444, USA.

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.

PMID:
19843957
PMCID:
PMC2778577
DOI:
10.1126/scisignal.2000599
[Indexed for MEDLINE]
Free PMC Article
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