Capillary cell-type specialization in the alveolus.

Capillary cell-type specialization in the alveolus.
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DOI:
10.1038/s41586-020-2822-7
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发表时间:
2020-10
期刊:
影响因子:
64.8
通讯作者:
Metzger RJ
Metzger RJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gillich A;Zhang F;Farmer CG;Travaglini KJ;Tan SY;Gu M;Zhou B;Feinstein JA;Krasnow MA;Metzger RJ

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在哺乳动物的肺中,每个肺泡周围都有一个明显均匀的毛细血管网,形成了巨大的呼吸表面,氧气通过这个表面转移到血液中。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,发展,更新和演变。我们发现肺泡毛细血管是镶嵌的;像内衬肺泡的上皮一样,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。我们称之为“气细胞”的一种细胞类型专门用于气体交换和白细胞运输,并且是肺所特有的。另一种称为gCap(一般毛细血管),专门调节血管紧张素,并在毛细血管稳态和修复中发挥干/祖细胞的作用。这两种细胞类型从双能祖细胞发育而来,它们逐渐成熟,并且在疾病和衰老中受到不同的影响。这种细胞类型特化在小鼠和人类之间是保守的,但在鳄鱼或海龟肺中没有发现,这表明在哺乳动物肺的进化过程中出现了特化的毛细血管细胞。毛细血管细胞类型特化的发现改变了我们对健康,疾病和进化中的空气-血液屏障和气体交换的结构,功能,调节和维护的理解。
In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to blood. 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; like the epithelium lining the alveolus, the alveolar endothelium is made up of two intermingled cell types, with complex ‘swiss cheese’-like morphologies and distinct functions. One cell type we term the ‘aerocyte’ is specialized for gas exchange and leukocyte trafficking, and unique to the lung. The other, 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, they mature gradually, and are affected differently in disease and aging. This cell type specialization is conserved between mouse and human but is not found in alligator or turtle lungs, suggesting that specialized capillary cells arose during evolution of the mammalian lung. The discovery of capillary cell type specialization transforms our understanding of the structure, function, regulation, and maintenance of the air-blood barrier and gas exchange in health, disease, and evolution.
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