The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi
Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2023
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| Online Access: | https://hdl.handle.net/10356/168660 |
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| author | Chan, Louisa L. Y. Anderson, Danielle E. Cheng, Hong Sheng Ivan, Fransiskus Xaverius Chen, Si Kang, Adrian E. Z. Foo, Randy Gamage, Akshamal M. Tiew, Pei Yee Koh, Mariko Siyue Lee, Ken Cheah Hooi Nichol, Kristy Pathinayake, Prabuddha S. Chan, Yik Lung Yeo, Tsin Wen Oliver, Brian G. Wark, Peter A. B. Liu, Linbo Tan, Nguan Soon Wang, Lin-Fa Chotirmall, Sanjay Haresh |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Chan, Louisa L. Y. Anderson, Danielle E. Cheng, Hong Sheng Ivan, Fransiskus Xaverius Chen, Si Kang, Adrian E. Z. Foo, Randy Gamage, Akshamal M. Tiew, Pei Yee Koh, Mariko Siyue Lee, Ken Cheah Hooi Nichol, Kristy Pathinayake, Prabuddha S. Chan, Yik Lung Yeo, Tsin Wen Oliver, Brian G. Wark, Peter A. B. Liu, Linbo Tan, Nguan Soon Wang, Lin-Fa Chotirmall, Sanjay Haresh |
| author_sort | Chan, Louisa L. Y. |
| collection | NTU |
| description | Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitulate disease at the individual level. In contrast to healthy organoids, goblet cell hyperplasia and reduced ciliary beat frequency were observed in COPD organoids, hallmark features of the disease. Single-cell transcriptomics uncovered evidence for altered cellular differentiation trajectories in COPD organoids. SARS-CoV-2 infection of COPD organoids revealed more productive replication in bronchi, the key site of infection in severe COVID-19. Viral and bacterial exposure of organoids induced greater pro-inflammatory responses in COPD organoids. In summary, we present an organoid model that recapitulates the in vivo physiological lung microenvironment at the individual level and is amenable to the study of host-pathogen interaction and emerging infectious disease. |
| first_indexed | 2024-10-01T05:18:04Z |
| format | Journal Article |
| id | ntu-10356/168660 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:18:04Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1686602023-06-16T15:40:08Z The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi Chan, Louisa L. Y. Anderson, Danielle E. Cheng, Hong Sheng Ivan, Fransiskus Xaverius Chen, Si Kang, Adrian E. Z. Foo, Randy Gamage, Akshamal M. Tiew, Pei Yee Koh, Mariko Siyue Lee, Ken Cheah Hooi Nichol, Kristy Pathinayake, Prabuddha S. Chan, Yik Lung Yeo, Tsin Wen Oliver, Brian G. Wark, Peter A. B. Liu, Linbo Tan, Nguan Soon Wang, Lin-Fa Chotirmall, Sanjay Haresh Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences School of Chemical and Biomedical Engineering School of Electrical and Electronic Engineering Science::Medicine Bronchi COVID-19 Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitulate disease at the individual level. In contrast to healthy organoids, goblet cell hyperplasia and reduced ciliary beat frequency were observed in COPD organoids, hallmark features of the disease. Single-cell transcriptomics uncovered evidence for altered cellular differentiation trajectories in COPD organoids. SARS-CoV-2 infection of COPD organoids revealed more productive replication in bronchi, the key site of infection in severe COVID-19. Viral and bacterial exposure of organoids induced greater pro-inflammatory responses in COPD organoids. In summary, we present an organoid model that recapitulates the in vivo physiological lung microenvironment at the individual level and is amenable to the study of host-pathogen interaction and emerging infectious disease. Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This research was supported by the National Research Foundation Singapore under its COVID-19 Research Fund administered by the Singapore Ministry of Health’s National Medical Research Council (MOH000409) (to S.H.C) and National Medical Research Council COVID19RF2-0006 (to L-F.W and D.E.A.) and by the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist Award (CSA) (MOH-000710) (S.H.C). 2023-06-13T08:06:59Z 2023-06-13T08:06:59Z 2022 Journal Article Chan, L. L. Y., Anderson, D. E., Cheng, H. S., Ivan, F. X., Chen, S., Kang, A. E. Z., Foo, R., Gamage, A. M., Tiew, P. Y., Koh, M. S., Lee, K. C. H., Nichol, K., Pathinayake, P. S., Chan, Y. L., Yeo, T. W., Oliver, B. G., Wark, P. A. B., Liu, L., Tan, N. S., ...Chotirmall, S. H. (2022). The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi. Nature Communications, 13(1), 7635-. https://dx.doi.org/10.1038/s41467-022-35253-x 2041-1723 https://hdl.handle.net/10356/168660 10.1038/s41467-022-35253-x 36496442 2-s2.0-85143695123 1 13 7635 en MOH000409 COVID19RF2-0006 MOH-000710 Nature Communications © 2022 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Medicine Bronchi COVID-19 Chan, Louisa L. Y. Anderson, Danielle E. Cheng, Hong Sheng Ivan, Fransiskus Xaverius Chen, Si Kang, Adrian E. Z. Foo, Randy Gamage, Akshamal M. Tiew, Pei Yee Koh, Mariko Siyue Lee, Ken Cheah Hooi Nichol, Kristy Pathinayake, Prabuddha S. Chan, Yik Lung Yeo, Tsin Wen Oliver, Brian G. Wark, Peter A. B. Liu, Linbo Tan, Nguan Soon Wang, Lin-Fa Chotirmall, Sanjay Haresh The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
| title | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
| title_full | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
| title_fullStr | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
| title_full_unstemmed | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
| title_short | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
| title_sort | establishment of copd organoids to study host pathogen interaction reveals enhanced viral fitness of sars cov 2 in bronchi |
| topic | Science::Medicine Bronchi COVID-19 |
| url | https://hdl.handle.net/10356/168660 |
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