Capillary cell-type specialization in the alveolus

被引:238
|
作者
Gillich, Astrid [1 ,2 ,3 ]
Zhang, Fan [4 ]
Farmer, Colleen G. [5 ]
Travaglini, Kyle J. [1 ,2 ,3 ,4 ]
Tan, Serena Y. [6 ]
Gu, Mingxia [3 ,4 ,7 ]
Zhou, Bin [8 ]
Feinstein, Jeffrey A. [3 ,4 ,7 ]
Krasnow, Mark A. [1 ,2 ,3 ,4 ]
Metzger, Ross J. [3 ,4 ,7 ]
机构
[1] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Vera Moulton Wall Ctr Pulm Vasc Dis, Stanford, CA 94305 USA
[5] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA
[6] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA USA
[7] Stanford Univ, Sch Med, Dept Pediat, Div Cardiol, Stanford, CA 94305 USA
[8] Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai, Peoples R China
基金
奥地利科学基金会; 美国国家科学基金会;
关键词
D O I
10.1038/s41586-020-2822-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 blood1. 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.
引用
收藏
页码:785 / +
页数:29
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