Spatially structured cell populations process multiple sensory signals in parallel in intact vascular endothelium

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Science Signaling  18 Dec 2018:
Vol. 11, Issue 561, eaar4411
DOI: 10.1126/scisignal.aar4411

Heterogeneity and cooperation in the endothelium

Endothelial cells lining blood vessels must sense, interpret, and respond to many different chemical signals. Coordination of the responses of these cells is critical for the proper function of the cardiovascular system. Lee et al. found that the coordinated behavior of endothelial cells in rat carotid artery resulted from communication between heterogeneous populations of cells with differential sensitivities to biochemical cues. Spatially distinct clusters of cells responded to either muscarinic or purinergic agonists; few cells were responsive to both. Each agonist evoked distinct intracellular signals, but communication between the different cell clusters generated new composite signals when both agonists were present. These results contribute to understanding how the endothelium can process large amounts of biochemical information for a coordinated, tissue-wide response.


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.

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