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Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells
Han Guangchun.
Sinjab Ansam.
Treekitkarnmongkol Warapen.
Brennan Patrick.
Hara Kieko.
Chang Kyle.
Bogatenkova Elena.
Sanchez-Espiridion Beatriz.
Behrens Carmen.
Gao Boning.
Girard Luc.
Zhang Jianjun.
Sepesi Boris.
Cascone Tina.
Byers Lauren.
Gibbons Don.
Chen Jichao.
Moghaddam Seyed Javad.
Ostrin Edwin.
Fujimoto Junya.
Shay Jerry.
Heymach John.
Minna John.
Dubinett Steven.
Scheet Paul.
Wistuba Ignacio.
Hill Edward.
Telesco Shannon.
Stevenson Christopher.
Spira Avrum.
Wang Linghua.
Kadara Humam.
Acceso Abierto
Atribución-NoComercial-SinDerivadas
10.1101/2020.04.16.045617
The novel coronavirus SARS-CoV-2 was identified as the causative agent of the ongoing pandemic COVID 19. COVID-19-associated deaths are mainly attributed to severe pneumonia and respiratory failure. Recent work demonstrated that SARS-CoV-2 binds to angiotensin converting enzyme 2 (ACE2) in the lung. To better understand ACE2 abundance and expression patterns in the lung we interrogated our in-house single-cell RNA-sequencing dataset containing 70,085 EPCAM+ lung epithelial cells from paired normal and lung adenocarcinoma tissues. Transcriptomic analysis revealed a diverse repertoire of airway lineages that included alveolar type I and II, bronchioalveolar, club/secretory, quiescent and proliferating basal, ciliated and malignant cells as well as rare populations such as ionocytes. While the fraction of lung epithelial cells expressing ACE2 was low (1.7% overall), alveolar type II (AT2, 2.2% ACE2 +) cells exhibited highest levels of ACE2 expression among all cell subsets. Further analysis of the AT2 compartment (n = 27,235 cells) revealed a number of genes co-expressed with ACE2 that are important for lung pathobiology including those associated with chronic obstructive pulmonary disease (COPD; HHIP ), pneumonia and infection ( FGG and C4BPA ) as well as malarial/bacterial ( CD36 ) and viral ( DMBT1 ) scavenging which, for the most part, were increased in smoker versus light or non-smoker cells. Notably, DMBT1 was highly expressed in AT2 cells relative to other lung epithelial subsets and its expression positively correlated with ACE2 . We describe a population of ACE2 -positive AT2 cells that co-express pathogen (including viral) receptors (e.g. DMBT1 ) with crucial roles in host defense thus comprising plausible phenotypic targets for treatment of COVID-19.
www.biorxiv.org
2020
Artículo
https://www.biorxiv.org/content/biorxiv/early/2020/04/17/2020.04.16.045617.full.pdf
Inglés
VIRUS RESPIRATORIOS
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