A cellular census of human lungs identifies novel cell states in health and in asthma

被引：584

作者：

Braga, Felipe A. Vieira ^{[1
,2
]}

Kar, Gozde ^{[1
,2
]}

Berg, Marijn ^{[3
,4
]}

Carpaij, Orestes A. ^{[4
,5
]}

Polanski, Krzysztof ^{[1
]}

Simon, Lukas M. ^{[6
]}

Brouwer, Sharon ^{[3
,4
]}

Gomes, Tomas ^{[1
]}

Hesse, Laura ^{[3
,4
]}

Jiang, Jian ^{[3
,4
]}

Fasouli, Eirini S. ^{[1
,2
]}

Efremova, Mirjana ^{[1
]}

Vento-Tormo, Roser ^{[1
]}

Talavera-Lopez, Carlos ^{[1
]}

Jonker, Marnix R. ^{[3
,4
]}

Affleck, Karen ^{[7
]}

Palit, Subarna ^{[6
,8
,9
,10
]}

Strzelecka, Paulina M. ^{[1
,11
,12
]}

Firth, Helen V. ^{[1
]}

Mahbubani, Krishnaa T. ^{[13
]}

Cvejic, Ana ^{[1
,11
,12
]}

Meyer, Kerstin B. ^{[1
]}

Saeb-Parsy, Kourosh ^{[13
]}

Luinge, Marjan ^{[3
,4
]}

Brandsma, Corry-Anke ^{[3
,4
]}

Timens, Wim ^{[3
,4
]}

Angelidis, Ilias ^{[14
]}

Strunz, Maximilian ^{[14
]}

Koppelman, Gerard H. ^{[4
,15
]}

van Oosterhout, Antoon J. ^{[7
]}

Schiller, Herbert B. ^{[14
]}

Theis, Fabian J. ^{[6
,16
]}

van den Berge, Maarten ^{[4
,5
]}

Nawijn, Martijn C. ^{[3
,4
]}

Teichmann, Sarah A. ^{[1
,2
,17
]}

机构：

[1] Wellcome Sanger Inst, Cambridge, England

[2] Open Targets, Cambridge, England

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen, Netherlands

[4] Univ Groningen, Univ Med Ctr Groningen, Groningen Res Inst Asthma & COPD, Groningen, Netherlands

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, Groningen, Netherlands

[6] Helmholtz Zentrum Munchen, Inst Computat Biol, Neuherberg, Germany

[7] GlaxoSmithKline, Allerg Inflammat Discovery Performance Unit, Resp Therapy Area, Stevenage, Herts, England

[8] Tech Univ Munich, TranslaTUM, Munich, Germany

[9] Tech Univ Munich, Inst Virol, Munich, Germany

[10] German Ctr Infect Res, Partner Site Munich, Munich, Germany

[11] Univ Cambridge, Dept Haematol, Cambridge, England

[12] Cambridge Stem Cell Inst, Cambridge, England

[13] Univ Cambridge, NIHR Cambridge Biomed Res Ctr, Dept Surg, Cambridge, England

[14] German Ctr Lung Res DZL, Inst Lung Biol & Dis, Helmholtz Zentrum Munchen, Munich, Germany

[15] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Pulmonol & Pediat Allergol, Groningen, Netherlands

[16] Tech Univ Munich, Dept Math, Garching, Germany

[17] Univ Cambridge, Dept Phys, Cavendish Lab, Condensed Matter Theory Grp, Cambridge, England

来源：

NATURE MEDICINE | 2019年 / 25卷 / 07期

基金：

英国惠康基金; 欧洲研究理事会;

关键词：

EPITHELIAL-CELLS; PROSTAGLANDIN D-2; RNA-SEQ; EXPRESSION; INFLAMMATION; PATHOGENESIS; MACROPHAGES; PHENOTYPE; DISEASE; GENE;

D O I：

10.1038/s41591-019-0468-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Human lungs enable efficient gas exchange and form an interface with the environment, which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single-cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in healthy lungs, and lower airways in asthmatic lungs. We report location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report the presence of pathogenic effector type 2 helper T cells (T(H)2) in asthmatic lungs and find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identifies a shift from airway structural cell communication in healthy lungs to a T(H)2-dominated interactome in asthmatic lungs.

引用

页码：1153 / +

页数：24

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