Epithelial Vegfa Specifies a Distinct Endothelial Population in the Mouse Lung.,Developmental Cell

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Epithelial Vegfa Specifies a Distinct Endothelial Population in the Mouse Lung.
Developmental Cell ( IF 10.7 ) Pub Date : 2020-02-13 , DOI: 10.1016/j.devcel.2020.01.009
Lisandra Vila Ellis ₁ , Margo P Cain ₂ , Vera Hutchison ₃ , Per Flodby ₄ , Edward D Crandall ₄ , Zea Borok ₄ , Bin Zhou ₅ , Edwin J Ostrin ₆ , Joshua D Wythe ₇ , Jichao Chen ₈

Affiliation

Department of Pulmonary Medicine, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA; Tecnológico de Monterrey - Escuela de Medicina, Monterrey 64710, Mexico.
Department of Pulmonary Medicine, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas M D Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Department of Pulmonary Medicine, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA; Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine and Hastings Center for Pulmonary Research, University of Southern California, Los Angeles, CA 90033, USA.
The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Department of Pulmonary Medicine, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA; Department of General Internal Medicine, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Department of Molecular Physiology and Biophysics, Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Pulmonary Medicine, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

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.

中文翻译：

上皮 Vegfa 在小鼠肺中指定了一个独特的内皮细胞群。

肺微血管系统对于气体交换至关重要，通常被认为是均质的。我们表明来自上皮细胞的 VEGFA 是小鼠肺中不同内皮细胞 (EC) 群体所必需的。Vegfa 主要由肺泡 1 型 (AT1) 细胞表达，并且局部需要指定 EC 的一个子集。单细胞 RNA 测序 (scRNA-seq) 表明，约 15% 的肺 ECs 在转录上是不同的——由碳酸酐酶 4 (Car4) 标记——并且如轨迹分析所表明的那样来自大量 ECs。Car4 ECs 具有广泛的细胞投射，并通过有限的基底膜与 AT1 细胞分离，没有干预周细胞。Car4 ECs 在上皮 Vegfa 缺失时特别丢失；没有 Car4 EC，尽管肌成纤维细胞外观正常，但肺泡空间异常扩大。肺 Car4 EC 和视网膜尖端 EC 具有共同和不同的特征。这些发现支持 AT1 细胞的信号传导作用并阐明肺泡发生。

更新日期：2020-02-20

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