In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to the blood 1 . Here we use single-cell analysis to elucidate the cell types, development, renewal and evolution of the alveolar capillary endothelium. We show that alveolar capillaries are mosaics; similar to the epithelium that lines the alveolus, the alveolar endothelium is made up of two intermingled cell types, with complex ‘Swiss-cheese’-like morphologies and distinct functions. The first cell type, which we term the ‘aerocyte’, is specialized for gas exchange and the trafficking of leukocytes, and is unique to the lung. The other cell type, termed gCap (‘general’ capillary), is specialized to regulate vasomotor tone, and functions as a stem/progenitor cell in capillary homeostasis and repair. The two cell types develop from bipotent progenitors, mature gradually and are affected differently in disease and during ageing. This cell-type specialization is conserved between mouse and human lungs but is not found in alligator or turtle lungs, suggesting it arose during the evolution of the mammalian lung. The discovery of cell type specialization in alveolar capillaries transforms our understanding of the structure, function, regulation and maintenance of the air–blood barrier and gas exchange in health, disease and evolution. Single-cell analysis of blood vessels in the alveolus, the site of chronic disease and virus-induced lung injury, reveals two intermingled endothelial cell types with specialized gas exchange and stem cell functions.

中文翻译：

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肺泡毛细血管细胞类型特化


在哺乳动物的肺部，每个肺泡周围都有明显均匀的毛细血管网，形成巨大的呼吸表面，氧气通过该表面转移到血液中 1 。在这里，我们使用单细胞分析来阐明肺泡毛细血管内皮的细胞类型、发育、更新和进化。我们证明肺泡毛细血管是马赛克的；与肺泡内衬的上皮类似，肺泡内皮由两种混合的细胞类型组成，具有复杂的“瑞士奶酪”样形态和独特的功能。第一种细胞类型，我们称之为“需氧细胞”，专门用于气体交换和白细胞运输，并且是肺部独有的。另一种细胞类型称为 gCap（“普通”毛细血管），专门调节血管舒缩张力，并在毛细血管稳态和修复中充当干细胞/祖细胞。这两种细胞类型由双能祖细胞发育而来，逐渐成熟，并在疾病和衰老过程中受到不同的影响。这种细胞类型的特化在小鼠和人类的肺部之间是保守的，但在鳄鱼或乌龟的肺部中没有发现，这表明它是在哺乳动物肺部的进化过程中出现的。肺泡毛细血管细胞类型特化的发现改变了我们对健康、疾病和进化中气血屏障和气体交换的结构、功能、调节和维护的理解。对肺泡（慢性疾病和病毒引起的肺损伤的部位）血管的单细胞分析揭示了两种具有特殊气体交换和干细胞功能的混合内皮细胞类型。