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Publication : Epithelial Vegfa Specifies a Distinct Endothelial Population in the Mouse Lung.

First Author  Vila Ellis L Year  2020
Journal  Dev Cell Volume  52
Issue  5 Pages  617-630.e6
PubMed ID  32059772 Mgi Jnum  J:297253
Mgi Id  MGI:6472541 Doi  10.1016/j.devcel.2020.01.009
Citation  Vila Ellis L, et al. (2020) Epithelial Vegfa Specifies a Distinct Endothelial Population in the Mouse Lung. Dev Cell 52(5):617-630.e6
abstractText  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 sequencing (scRNA-seq) reveals that approximately 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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