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.
Dev Cell. 2020 Mar 9;52(5):617-630.e6. doi: 10.1016/j.devcel.2020.01.009. Epub 2020 Feb 13.
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.
肺微血管对于气体交换至关重要，通常被认为是均匀的。我们发现，上皮细胞中的 VEGFA 对于小鼠肺部的一个独特的内皮细胞（EC）群体是必需的。Vegfa 主要由肺泡 I 型（AT1）细胞表达，并在局部特异性指定一组 ECs。单细胞 RNA 测序（scRNA-seq）揭示了约 15%的肺 ECs 在转录上是不同的——由碳酸酐酶 4（Car4）标记——并由批量 ECs 产生，这一点可以通过轨迹分析来推测。Car4 ECs 具有广泛的细胞突起，并且与 AT1 细胞之间有一层有限的基底膜，没有中间的周细胞。上皮细胞 Vegfa 缺失后，Car4 ECs 会特异性丢失；没有 Car4 ECs，尽管肌成纤维细胞的外观正常，肺泡空间仍会异常增大。肺 Car4 ECs 和视网膜尖端 ECs 具有共同和独特的特征。这些发现支持了 AT1 细胞的信号作用，并阐明了肺泡发生。
