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Spatially structured cell populations process multiple sensory signals in parallel in intact vascular endothelium
Science Signaling ( IF 6.7 ) Pub Date : 2018-12-18 , DOI: 10.1126/scisignal.aar4411
Matthew D Lee 1 , Calum Wilson 1 , Christopher D Saunter 2 , Charles Kennedy 1 , John M Girkin 2 , John G McCarron 1
Affiliation  

Blood flow, blood clotting, angiogenesis, vascular permeability, and vascular remodeling are each controlled by a large number of variable, noisy, and interacting chemical inputs to the vascular endothelium. The endothelium processes the entirety of the chemical composition to which the cardiovascular system is exposed, carrying out sophisticated computations that determine physiological output. Processing this enormous quantity of information is a major challenge facing the endothelium. We analyzed the responses of hundreds of endothelial cells to carbachol (CCh) and adenosine triphosphate (ATP) and found that the endothelium segregates the responses to these two distinct components of the chemical environment into separate streams of complementary information that are processed in parallel. Sensitivities to CCh and ATP mapped to different clusters of cells, and each agonist generated distinct signal patterns. The distinct signals were features of agonist activation rather than properties of the cells themselves. When there was more than one stimulus present, the cells communicated and combined inputs to generate new distinct signals that were nonlinear combinations of the inputs. Our results demonstrate that the endothelium is a structured, collaborative sensory network that simplifies the complex environment using separate cell clusters that are sensitive to distinct aspects of the overall biochemical environment and interactively compute signals from diverse but interrelated chemical inputs. These features enable the endothelium to selectively process separate signals and perform multiple computations in an environment that is noisy and variable.



中文翻译:

空间结构化的细胞群在完整的血管内皮中并行处理多个感觉信号

血流、血液凝固、血管生成、血管通透性和血管重塑均由血管内皮的大量可变、嘈杂和相互作用的化学输入控制。内皮处理心血管系统所暴露的全部化学成分,进行复杂的计算以确定生理输出。处理如此大量的信息是内皮细胞面临的主要挑战。我们分析了数百个内皮细胞对卡巴胆碱 (CCh) 和三磷酸腺苷 (ATP) 的反应,发现内皮细胞将对化学环境的这两种不同成分的反应分离成并行处理的独立互补信息流。对 CCh 和 ATP 的敏感性映射到不同的细胞簇,并且每种激动剂产生不同的信号模式。不同的信号是激动剂激活的特征,而不是细胞本身的特性。当存在不止一种刺激时,细胞会进行交流并组合输入以生成新的不同信号,这些信号是输入的非线性组合。我们的研究结果表明,内皮是一个结构化的、协作的感觉网络,它使用单独的细胞簇来简化复杂的环境,这些细胞簇对整个生化环境的不同方面敏感,并交互式地计算来自不同但相互关联的化学输入的信号。

更新日期:2018-12-19
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