Nov 13, 2019

Epithelial Vegfa specifies a distinct endothelial population in the mouse lung

BioRxiv : the Preprint Server for Biology
Lisandra Vila EllisJichao Chen


The lung microvasculature is essential for gas exchange and commonly considered homogeneous. We show that VEGFA from the epithelium is required for a distinct endothelial cell (EC) population in the mouse lung. Vegfa is predominantly expressed by alveolar type 1 (AT1) cells and locally required to specify a subset of ECs. Single cell RNA-seq reveals that ~15% of lung ECs are transcriptionally distinct - marked by Carbonic anhydrase 4 (Car4) - and arise from bulk ECs, as suggested by trajectory analysis. Car4 ECs have extensive cellular projections and are separated from AT1 cells by a limited basement membrane without intervening pericytes. Car4 ECs are specifically lost upon epithelial Vegfa deletion; without Car4 ECs, the alveolar space is aberrantly enlarged despite the normal appearance of myofibroblasts. Lung Car4 ECs and retina tip ECs have common and distinct features. These findings support a signaling role of AT1 cells and shed light on alveologenesis.

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Mentioned in this Paper

Single-Cell Analysis
VEGFA gene
Gene Deletion
Pulmonary Gas Exchange
Electronic Cigarettes

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