Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells
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 hig...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38548-1 |
| _version_ | 1797774230579838976 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Shohei Minami |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T22:18:01Z |
| format | Article |
| id | doaj.art-87258b246f2a436185b38dcf74f2a65a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T22:18:01Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-87258b246f2a436185b38dcf74f2a65a2023-07-23T11:14:07ZengNature PortfolioScientific Reports2045-23222023-07-0113111010.1038/s41598-023-38548-1Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cellsShohei Minami0Naomi Matsumoto1Hiroko Omori2Yutaka Nakamura3Shigeyuki Tamiya4Ryotaro Nouda5Jeffery A. Nurdin6Moeko Yamasaki7Tomohiro Kotaki8Yuta Kanai9Toru Okamoto10Taro Tachibana11Hiroshi Ushijima12Takeshi Kobayashi13Shintaro Sato14Department of Virology, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Virology, Research Institute for Microbial Diseases, Osaka UniversityCore Instrumentation Facility, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical UniversityDepartment of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical UniversityDepartment of Virology, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Virology, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Virology, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Virology, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Virology, Research Institute for Microbial Diseases, Osaka UniversityInstitute for Advanced Co-creation Studies, Research Institute for Microbial Diseases, Osaka UniversityCell Engineering CorporationDivision of Microbiology, Department of Pathology and Microbiology, Nihon University School of MedicineDepartment of Virology, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Virology, Research Institute for Microbial Diseases, Osaka UniversityAbstract 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.https://doi.org/10.1038/s41598-023-38548-1 |
| spellingShingle | 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 Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells Scientific Reports |
| title | Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells |
| title_full | Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells |
| title_fullStr | Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells |
| title_full_unstemmed | Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells |
| title_short | Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells |
| title_sort | effective sars cov 2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells |
| url | https://doi.org/10.1038/s41598-023-38548-1 |
| work_keys_str_mv | AT shoheiminami effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT naomimatsumoto effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT hirokoomori effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT yutakanakamura effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT shigeyukitamiya effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT ryotaronouda effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT jefferyanurdin effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT moekoyamasaki effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT tomohirokotaki effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT yutakanai effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT toruokamoto effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT tarotachibana effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT hiroshiushijima effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT takeshikobayashi effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells AT shintarosato effectivesarscov2replicationofmonolayersofintestinalepithelialcellsdifferentiatedfromhumaninducedpluripotentstemcells |