Processing stimulus dynamics by the NF-κB network in single cells.
Processing stimulus dynamics by the NF-κB network in single cells.
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DOI：
10.1038/s12276-023-01133-7
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发表时间：
2023-12
影响因子：
12.8
通讯作者：
Tay, Savas
中科院分区：
文献类型：
--
作者：
Son, Minjun;Wang, Andrew G.;Keisham, Bijentimala;Tay, Savas
感染部位的细胞会经历许多在振幅、空间和时间上变化的生化信号。尽管病原体和前哨细胞产生的动态信号多种多样，但信息处理途径集中在有限数量的中心信号节点上，最终控制细胞反应。特别是，NF-κB通路对来自病原体和自身的数十种信号作出反应，并在处理促炎输入中发挥重要作用。由于活细胞测量的技术限制，针对刺激动力学对NF-κB信号传导影响的研究很少。然而，微流体、自动化和图像分析的最新进展使研究能够在单细胞水平上产生高时间分辨率。在此，我们总结了近年来关于测量和模拟NF-κB对脉动和波动刺激浓度以及不同信号分子组合和序列的反应的研究。总的来说，这些研究表明NF-κB网络整合外部炎症信号并将其转化为下游转录反应。Minjun Son的研究重点是NF-κB（一种控制炎症反应的中心转录因子）在不同刺激动态和组合下的复杂调控。这些刺激包括细胞因子（用于细胞-细胞信号传导的小分泌蛋白）和病原体的其他分泌物。虽然确切的机制尚不清楚，但以前和正在进行的研究已经努力阐明NF-κB对短脉冲、波动或刺激组合的反应。通过先进的技术和分析方法，研究人员发现NF-κB反应受刺激的动态和组合的显著影响。NF-κB反应的差异导致了不同的基因表达模式，强调了NF-κB通路在解释信号分子动力学和决定细胞行为方面的关键作用。未来使用小鼠模型的研究将弥合这些实验结果与体内生理过程之间的差距。本摘要最初是使用人工智能起草的，然后由作者进行修改和事实核查。
Cells at the site of an infection experience numerous biochemical signals that vary in amplitude, space, and time. Despite the diversity of dynamic signals produced by pathogens and sentinel cells, information-processing pathways converge on a limited number of central signaling nodes to ultimately control cellular responses. In particular, the NF-κB pathway responds to dozens of signals from pathogens and self, and plays a vital role in processing proinflammatory inputs. Studies addressing the influence of stimulus dynamics on NF-κB signaling are rare due to technical limitations with live-cell measurements. However, recent advances in microfluidics, automation, and image analysis have enabled investigations that yield high temporal resolution at the single-cell level. Here, we summarize the recent research which measures and models the NF-κB response to pulsatile and fluctuating stimulus concentrations, as well as different combinations and sequences of signaling molecules. Collectively, these studies show that the NF-κB network integrates external inflammatory signals and translates these into downstream transcriptional responses. Minjun Son’s research focuses on the intricate regulation of NF-κB, a central transcription factor governing inflammatory responses, under diverse stimulus dynamics and combinations. These stimuli include cytokines (small secreted proteins for cell-cell signaling) and other secretions from pathogens. While the precise mechanisms remain unknown, previous and ongoing studies have endeavored to elucidate NF-κB’s response to short bursts, fluctuations, or combinations of stimuli. Through advanced technologies and analytical methods, researchers discovered that the NF-κB response is significantly influenced by the dynamics and combinations of stimuli. This variance in NF-κB response resulted in distinct gene expression patterns, underscoring the pivotal role of the NF-κB pathway in interpreting the dynamics of signal molecules and determining cell behavior. Future studies employing mouse models would bridge the gap between these experimental findings and physiological processes in vivo. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
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