The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi
© 2022. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Nature communications - 13(2022), 1 vom: 10. Dez., Seite 7635 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chan, Louisa L Y [VerfasserIn] |
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| Anmerkungen: |
Date Completed 16.12.2022 Date Revised 21.12.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-022-35253-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Chan, Louisa L Y |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
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| 520 | |a © 2022. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Anderson, Danielle E |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Hong Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ivan, Fransiskus Xaverius |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Si |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Adrian E Z |e verfasserin |4 aut | |
| 700 | 1 | |a Foo, Randy |e verfasserin |4 aut | |
| 700 | 1 | |a Gamage, Akshamal M |e verfasserin |4 aut | |
| 700 | 1 | |a Tiew, Pei Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Koh, Mariko Siyue |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Ken Cheah Hooi |e verfasserin |4 aut | |
| 700 | 1 | |a Nichol, Kristy |e verfasserin |4 aut | |
| 700 | 1 | |a Pathinayake, Prabuddha S |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Yik Lung |e verfasserin |4 aut | |
| 700 | 1 | |a Yeo, Tsin Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Oliver, Brian G |e verfasserin |4 aut | |
| 700 | 1 | |a Wark, Peter A B |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Linbo |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Nguan Soon |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lin-Fa |e verfasserin |4 aut | |
| 700 | 1 | |a Chotirmall, Sanjay H |e verfasserin |4 aut | |
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