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

SARS-CoV-2 在由人类诱导性多能干细胞分化而来的肠上皮细胞单层中的有效复制

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作者:Shohei Minami, Naomi Matsumoto, Hiroko Omori, Yutaka Nakamura, Shigeyuki Tamiya, Ryotaro Nouda, Jeffery A Nurdin, Moeko Yamasaki, Tomohiro Kotaki, Yuta Kanai, Toru Okamoto, Taro Tachibana, Hiroshi Ushijima, Takeshi Kobayashi, Shintaro Sato

Abstract

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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