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About:
Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection and Drug Test
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schema:ScholarlyArticle
, within Data Space :
covidontheweb.inria.fr
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document(s)
Type:
Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
title
Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection and Drug Test
Creator
Xiao, Shuqi
Li, Lian
Lin, Ying
Wen, Kun
Chen, Xinwen
Pei, Rongjuan
Sun, Hao
Xiong, Jin
Zhou, Hongwei
Chen, Jiekai
Feng, Jianqi
He, Jiangping
Rong, Zhili
Yang, Xuejie
Zhang, Yecheng
source
BioRxiv
abstract
The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we demonstrated that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids. Ciliated cells, alveolar type 2 (AT2) cells and rare club cells were virus target cells. Electron microscopy captured typical replication, assembly and release ultrastructures and revealed the presence of viruses within lamellar bodies in AT2 cells. Virus infection induced more severe cell death in alveolar organoids than in airway organoids. Additionally, RNA-seq revealed early cell response to SARS-CoV-2 infection and an unexpected downregulation of ACE2 mRNA. Further, compared to the transmembrane protease, serine 2 (TMPRSS2) inhibitor camostat, the nucleotide analog prodrug Remdesivir potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model for SARS-CoV-2 infection and drug discovery.
has issue date
2020-08-10
(
xsd:dateTime
)
bibo:doi
10.1101/2020.08.10.244350
has license
biorxiv
sha1sum (hex)
bc8e62cf1bdd3f883493796d8ccfdce26f57fa6d
schema:url
https://doi.org/10.1101/2020.08.10.244350
resource representing a document's title
Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection and Drug Test
schema:publication
bioRxiv
resource representing a document's body
covid:bc8e62cf1bdd3f883493796d8ccfdce26f57fa6d#body_text
is
schema:about
of
named entity 'typical'
named entity 'physiological'
named entity 'organoids'
named entity 'cells'
named entity 'AT2'
named entity 'cancer'
named entity 'infection'
named entity 'infects'
named entity 'infected'
named entity 'PANDEMIC'
named entity 'CELL LINES'
named entity 'PROTEASE'
named entity 'RARE'
named entity 'MRNA'
named entity 'CORONAVIRUS DISEASE 2019'
named entity 'SARS-COV-2 INFECTION'
named entity 'INFECTION'
named entity 'SERINE'
named entity 'VIRUSES'
covid:arg/bc8e62cf1bdd3f883493796d8ccfdce26f57fa6d
named entity 'organoids'
named entity 'alveolar'
named entity 'alveolar'
named entity 'replication'
named entity 'respiratory droplets'
named entity 'coronavirus disease 2019'
named entity 'cell lines'
named entity 'organoids'
named entity 'replication'
named entity 'stem'
named entity 'club cells'
named entity 'serine'
named entity 'Test'
named entity 'organoids'
named entity 'lungs'
named entity 'cell lines'
named entity 'coronavirus disease 2019'
named entity 'respiratory droplets'
named entity 'RNA-seq'
named entity 'cancer cells'
named entity 'SARS-CoV-2'
named entity 'Electron microscopy'
named entity 'airway'
named entity 'club cells'
named entity 'prodrug'
named entity 'cell lines'
named entity 'SARS-CoV-2'
named entity 'Lung'
named entity 'Human Embryonic Stem Cell'
named entity 'virus receptor'
named entity 'endoderm'
named entity 'dehydrated'
named entity 'type 2'
named entity 'camostat'
named entity 'SARS-CoV-2'
named entity 'protein'
named entity 'nucleotide analogue'
named entity 'human lung'
named entity 'Organoids'
named entity 'hpi'
named entity 'viral RNA'
named entity 'membrane vesicles'
named entity 'Ki67'
named entity 'COVID-19'
named entity 'virus'
named entity 'hpi'
named entity 'serine protease'
named entity 'Caco-2'
named entity 'SARS-CoV-2'
named entity 'bestatin'
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