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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 ∼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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Lisandra Vila Ellis, Margo P Cain, Vera Hutchison, Per Flodby, Edward D Crandall, Zea Borok, Bin Zhou, Edwin J Ostrin, Joshua D Wythe, Jichao Chen. Epithelial Vegfa Specifies a Distinct Endothelial Population in the Mouse Lung. Developmental cell. 2020 Mar 09;52(5):617-630.e6

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PMID: 32059772

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