A Noisy Paracrine Signal Determines the Cellular NF-κB Response to Lipopolysaccharide
A Noisy Paracrine Signal Determines the Cellular NF-κB Response to Lipopolysaccharide
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DOI：
10.1126/scisignal.2000599
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发表时间：
2009-10-20
影响因子：
7.3
通讯作者：
Covert, Markus W.
中科院分区：
文献类型：
--
作者：
Lee, Timothy K.;Denny, Elissa M.;Covert, Markus W.
几乎相同的细胞可以表现出对相同刺激的大幅不同的反应。我们监测了肿瘤坏死因子-Alpha（TNF-Alpha）和脂多糖（LPS）刺激的单细胞中核因子KAPPA B（NF-KAPPA B）的核定位动力学。用TNF-α刺激的细胞在NF-kappa B核定位上具有定量差异，而LPS刺激的细胞可以聚集成瞬态或持续的响应者，根据NF-KAPPA B反应代表两个定性不同的组。这些不同的行为可以与低浓度下分泌的次生旁分泌信号相关，因此并非所有细胞都会经历第二轮NF-kappa b激活。从我们的单细胞数据中，我们构建了一个捕获细胞变异性以及人群行为的计算模型。我们的发现表明，哺乳动物细胞可以创建“嘈杂”的环境，以产生对刺激的多样化反应。
Nearly identical cells can exhibit substantially different responses to the same stimulus. We monitored the nuclear localization dynamics of nuclear factor kappa B (NF-kappa B) in single cells stimulated with tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS). Cells stimulated with TNF-alpha have quantitative differences in NF-kappa B nuclear localization, whereas LPS-stimulated cells can be clustered into transient or persistent responders, representing two qualitatively different groups based on the NF-kappa B 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-kappa B 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.