| First Author | Lee TK | Year | 2009 |
| Journal | Sci Signal | Volume | 2 |
| Issue | 93 | Pages | ra65 |
| PubMed ID | 19843957 | Mgi Jnum | J:260203 |
| Mgi Id | MGI:6142706 | Doi | 10.1126/scisignal.2000599 |
| Citation | Lee TK, et al. (2009) A noisy paracrine signal determines the cellular NF-kappaB response to lipopolysaccharide. Sci Signal 2(93):ra65 |
| abstractText | 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. |
