TY - JOUR
T1 - Single-cell expression landscape of SARS-CoV-2 receptor ACE2 and host proteases in normal and malignant lung tissues from pulmonary adenocarcinoma patients
AU - Han, Guangchun
AU - Sinjab, Ansam
AU - Hara, Kieko
AU - Treekitkarnmongkol, Warapen
AU - Brennan, Patrick
AU - Chang, Kyle
AU - Bogatenkova, Elena
AU - Sanchez Espiridion, Beatriz
AU - Behrens, Carmen
AU - Solis, Luisa M.
AU - Gao, Boning
AU - Girard, Luc
AU - Zhang, Jianjun
AU - Sepesi, Boris
AU - Cascone, Tina
AU - Byers, Lauren A.
AU - Gibbons, Don L.
AU - Chen, Jichao
AU - Moghaddam, Seyed Javad
AU - Ostrin, Edwin J.
AU - Scheet, Paul
AU - Fujimoto, Junya
AU - Shay, Jerry
AU - Heymach, John V.
AU - Minna, John D.
AU - Dubinett, Steven
AU - Wistuba, Ignacio I.
AU - Stevenson, Christopher S.
AU - Spira, Avrum E.
AU - Wang, Linghua
AU - Kadara, Humam
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/3/2
Y1 - 2021/3/2
N2 - The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of ACE2 and SARS-CoV-2-priming proteases TMPRSS2 and TMPRSS4 in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of ACE2, TMPRSS2, and TMPRSS4. Analysis of 70,030 LUAD-and normal-derived epithelial cells showed that ACE2 levels were highest in normal alveolar type 2 (AT2) cells and that TMPRSS2 was expressed in 65% of normal AT2 cells. Conversely, the expression of TMPRSS4 was highest and most frequently detected (75%) in lung cells with malignant features. ACE2-positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated HHIP, and the scavengers CD36 and DMBT1. Notably, the viral scavenger DMBT1 was significantly positively correlated with ACE2 expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.
AB - The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of ACE2 and SARS-CoV-2-priming proteases TMPRSS2 and TMPRSS4 in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of ACE2, TMPRSS2, and TMPRSS4. Analysis of 70,030 LUAD-and normal-derived epithelial cells showed that ACE2 levels were highest in normal alveolar type 2 (AT2) cells and that TMPRSS2 was expressed in 65% of normal AT2 cells. Conversely, the expression of TMPRSS4 was highest and most frequently detected (75%) in lung cells with malignant features. ACE2-positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated HHIP, and the scavengers CD36 and DMBT1. Notably, the viral scavenger DMBT1 was significantly positively correlated with ACE2 expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.
KW - Alveolar epithelial cells
KW - COVID-19
KW - Lung neoplasms
KW - Single-cell RNA sequencing
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U2 - 10.3390/cancers13061250
DO - 10.3390/cancers13061250
M3 - Article
C2 - 33809063
AN - SCOPUS:85102376191
SN - 2072-6694
VL - 13
SP - 1
EP - 13
JO - Cancers
JF - Cancers
IS - 6
M1 - 1250
ER -