Establishment of a bat lung organoid culture model for studying bat-derived infectious diseases

Abstract Bat is considered a natural reservoir of various important pathogens, including severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, Ebola virus, and Nipah virus. To study these viruses’ pathogenicity and proliferation efficacy and viral tolerance mechanisms in bats, bat-de...

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Main Authors: Mohamed Elbadawy, Nagisa Saito, Yuki Kato, Kimika Hayashi, Amira Abugomaa, Mio Kobayashi, Toshinori Yoshida, Makoto Shibutani, Masahiro Kaneda, Hideyuki Yamawaki, Kazuaki Sasaki, Tatsuya Usui, Tsutomu Omatsu
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-88621-0
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author Mohamed Elbadawy
Nagisa Saito
Yuki Kato
Kimika Hayashi
Amira Abugomaa
Mio Kobayashi
Toshinori Yoshida
Makoto Shibutani
Masahiro Kaneda
Hideyuki Yamawaki
Kazuaki Sasaki
Tatsuya Usui
Tsutomu Omatsu
author_facet Mohamed Elbadawy
Nagisa Saito
Yuki Kato
Kimika Hayashi
Amira Abugomaa
Mio Kobayashi
Toshinori Yoshida
Makoto Shibutani
Masahiro Kaneda
Hideyuki Yamawaki
Kazuaki Sasaki
Tatsuya Usui
Tsutomu Omatsu
author_sort Mohamed Elbadawy
collection DOAJ
description Abstract Bat is considered a natural reservoir of various important pathogens, including severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, Ebola virus, and Nipah virus. To study these viruses’ pathogenicity and proliferation efficacy and viral tolerance mechanisms in bats, bat-derived cell lines, and primary cultured cells are used. However, these do not adequately reflect the exact biology of bats, and establishing new bat-related research models is necessary. Organoid culture can recapitulate organ structure, functions, and diseases. The respiratory tract is one of the primary routes of viral infection, and the establishment of bat lung organoids (BLO) is necessary to study the viral susceptibility in bats. Therefore, we aimed to establish a culture method of BLO from Rousettus leschenaultia that died of natural causes. The generated BLO successfully recapitulated the characteristics of pulmonary epithelial structure and morphology. BLO expressed the entry receptors for coronavirus, Angiotensin-converting enzyme 2 (ACE2), and Transmembrane Protease Serine 2 (TMPRSS2), and alveolar type 2 cells were successfully sorted from BLO, which has an important role for the development of viral infection in the respiratory system. Furthermore, we showed that BLO had no susceptibility to Pteropine orthoreovirus (PRV) compared to bat intestinal organoids. Collectively, our established bat organoid culture models including this BLO might become promising in vitro biomaterials to study the biology of bat-derived infectious diseases.
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spelling doaj-art-a0f0cc285a3b461abc94430a80f092c62025-02-09T12:36:01ZengNature PortfolioScientific Reports2045-23222025-02-0115111310.1038/s41598-025-88621-0Establishment of a bat lung organoid culture model for studying bat-derived infectious diseasesMohamed Elbadawy0Nagisa Saito1Yuki Kato2Kimika Hayashi3Amira Abugomaa4Mio Kobayashi5Toshinori Yoshida6Makoto Shibutani7Masahiro Kaneda8Hideyuki Yamawaki9Kazuaki Sasaki10Tatsuya Usui11Tsutomu Omatsu12Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyResearch and Education Center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and TechnologyResearch and Education Center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Anatomy, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato UniversityLaboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyLaboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyResearch and Education Center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and TechnologyAbstract Bat is considered a natural reservoir of various important pathogens, including severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, Ebola virus, and Nipah virus. To study these viruses’ pathogenicity and proliferation efficacy and viral tolerance mechanisms in bats, bat-derived cell lines, and primary cultured cells are used. However, these do not adequately reflect the exact biology of bats, and establishing new bat-related research models is necessary. Organoid culture can recapitulate organ structure, functions, and diseases. The respiratory tract is one of the primary routes of viral infection, and the establishment of bat lung organoids (BLO) is necessary to study the viral susceptibility in bats. Therefore, we aimed to establish a culture method of BLO from Rousettus leschenaultia that died of natural causes. The generated BLO successfully recapitulated the characteristics of pulmonary epithelial structure and morphology. BLO expressed the entry receptors for coronavirus, Angiotensin-converting enzyme 2 (ACE2), and Transmembrane Protease Serine 2 (TMPRSS2), and alveolar type 2 cells were successfully sorted from BLO, which has an important role for the development of viral infection in the respiratory system. Furthermore, we showed that BLO had no susceptibility to Pteropine orthoreovirus (PRV) compared to bat intestinal organoids. Collectively, our established bat organoid culture models including this BLO might become promising in vitro biomaterials to study the biology of bat-derived infectious diseases.https://doi.org/10.1038/s41598-025-88621-0BatRousettus leschenaultiiLung organoidACE2TMPRSS2Alveolar type 2 cells
spellingShingle Mohamed Elbadawy
Nagisa Saito
Yuki Kato
Kimika Hayashi
Amira Abugomaa
Mio Kobayashi
Toshinori Yoshida
Makoto Shibutani
Masahiro Kaneda
Hideyuki Yamawaki
Kazuaki Sasaki
Tatsuya Usui
Tsutomu Omatsu
Establishment of a bat lung organoid culture model for studying bat-derived infectious diseases
Scientific Reports
Bat
Rousettus leschenaultii
Lung organoid
ACE2
TMPRSS2
Alveolar type 2 cells
title Establishment of a bat lung organoid culture model for studying bat-derived infectious diseases
title_full Establishment of a bat lung organoid culture model for studying bat-derived infectious diseases
title_fullStr Establishment of a bat lung organoid culture model for studying bat-derived infectious diseases
title_full_unstemmed Establishment of a bat lung organoid culture model for studying bat-derived infectious diseases
title_short Establishment of a bat lung organoid culture model for studying bat-derived infectious diseases
title_sort establishment of a bat lung organoid culture model for studying bat derived infectious diseases
topic Bat
Rousettus leschenaultii
Lung organoid
ACE2
TMPRSS2
Alveolar type 2 cells
url https://doi.org/10.1038/s41598-025-88621-0
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