Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe acute respiratory symptoms in humans. Controlling the coronavirus disease pandemic is a worldwide priority. The number of SARS-CoV-2 studies has dramatically increased, and the requirement for analytical tools is higher than...

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Published inScientific reports Vol. 13; no. 1; p. 11610
Main Authors Minami, Shohei, Matsumoto, Naomi, Omori, Hiroko, Nakamura, Yutaka, Tamiya, Shigeyuki, Nouda, Ryotaro, Nurdin, Jeffery A., Yamasaki, Moeko, Kotaki, Tomohiro, Kanai, Yuta, Okamoto, Toru, Tachibana, Taro, Ushijima, Hiroshi, Kobayashi, Takeshi, Sato, Shintaro
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 18.07.2023
Nature Publishing Group
Nature Portfolio
Subjects
631/326/596/4130
692/308/1426
692/420/254
ACE2
Angiotensin
Angiotensin-converting enzyme 2
Cell differentiation
Coronaviruses
COVID-19
Disease transmission
Enzymes
Epithelial Cells
Humanities and Social Sciences
Humans
Induced Pluripotent Stem Cells
Infections
Intestine
Intestines
multidisciplinary
Organoids
Pandemics
Peptidyl-dipeptidase A
Pluripotency
Propagation
Protein expression
Proteins
Research centers
SARS-CoV-2
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Stem cells
Viruses
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Summary:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe acute respiratory symptoms in humans. Controlling the coronavirus disease pandemic is a worldwide priority. The number of SARS-CoV-2 studies has dramatically increased, and the requirement for analytical tools is higher than ever. Here, we propose monolayered-intestinal epithelial cells (IECs) derived from human induced pluripotent stem cells (iPSCs) instead of three-dimensional cultured intestinal organoids as a suitable tool to study SARS-CoV-2 infection. Differentiated IEC monolayers express high levels of angiotensin-converting enzyme 2 and transmembrane protease serine 2 (TMPRSS2), host factors essential for SARS-CoV-2 infection. SARS-CoV-2 efficiently grows in IEC monolayers. Using this propagation system, we confirm that TMPRSS2 inhibition blocked SARS-CoV-2 infection in IECs. Hence, our iPSC-derived IEC monolayers are suitable for SARS-CoV-2 research under physiologically relevant conditions.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-38548-1