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The Endothelium Solves Problems That Endothelial Cells Do Not Know Exist.

ABSTRACT: The endothelium is the single layer of cells that lines the entire cardiovascular system and regulates vascular tone and blood-tissue exchange, recruits blood cells, modulates blood clotting, and determines the formation of new blood vessels. To control each function, the endothelium uses a remarkable sensory capability to continuously monitor vanishingly small changes in the concentrations of many simultaneously arriving extracellular activators that each provides cues to the physiological state. Here we suggest that the extraordinary sensory capabilities of the endothelium do not come from single cells but from the combined activity of a large number of endothelial cells. Each cell has a limited, but distinctive, sensory capacity and shares information with neighbours so that sensing is distributed among cells. Communication of information among connected cells provides system-level sensing substantially greater than the capabilities of any single cell and, as a collective, the endothelium solves sensory problems too complex for any single cell.

SUBMITTER: McCarron JG

PROVIDER: S-EPMC5381697 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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The Endothelium Solves Problems That Endothelial Cells Do Not Know Exist.

McCarron John G JG Lee Matthew D MD Wilson Calum C

Trends in pharmacological sciences 20170216 4

The endothelium is the single layer of cells that lines the entire cardiovascular system and regulates vascular tone and blood-tissue exchange, recruits blood cells, modulates blood clotting, and determines the formation of new blood vessels. To control each function, the endothelium uses a remarkable sensory capability to continuously monitor vanishingly small changes in the concentrations of many simultaneously arriving extracellular activators that each provides cues to the physiological stat ...[more]

PMID: 28214012

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Project description:The renal endothelium has been debated as arising from resident hemangioblast precursors that transdifferentiate from the nephrogenic mesenchyme (vasculogenesis) and/or from invading vessels (angiogenesis). While the Foxd1-positive renal cortical stroma has been shown to differentiate into cells that support the vasculature in the kidney (including vascular smooth muscle and pericytes) it has not been considered as a source of endothelial cell progenitors. In addition, it is unclear if Foxd1-positive mesenchymal cells in other organs such as the lung have the potential to form endothelium. This study examines the potential for Foxd1-positive cells of the kidney and lung to give rise to endothelial progenitors. We utilized immunofluorescence (IF) and fluorescence-activated cell sorting (FACS) to co-label Foxd1-expressing cells (including permanently lineage-tagged cells) with endothelial markers in embryonic and postnatal mice. We also cultured FACsorted Foxd1-positive cells, performed in vitro endothelial cell tubulogenesis assays and examined for endocytosis of acetylated low-density lipoprotein (Ac-LDL), a functional assay for endothelial cells. Immunofluorescence and FACS revealed that a subset of Foxd1-positive cells from kidney and lung co-expressed endothelial cell markers throughout embryogenesis. In vitro, cultured embryonic Foxd1-positive cells were able to differentiate into tubular networks that expressed endothelial cell markers and were able to endocytose Ac-LDL. IF and FACS in both the kidney and lung revealed that lineage-tagged Foxd1-positive cells gave rise to a significant portion of the endothelium in postnatal mice. In the kidney, the stromal-derived cells gave rise to a portion of the peritubular capillary endothelium, but not of the glomerular or large vessel endothelium. These findings reveal the heterogeneity of endothelial cell lineages; moreover, Foxd1-positive mesenchymal cells of the developing kidney and lung are a source of endothelial progenitors that are likely critical to patterning the vasculature.

Dataset Information

The Endothelium Solves Problems That Endothelial Cells Do Not Know Exist.

Publications

The Endothelium Solves Problems That Endothelial Cells Do Not Know Exist.

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