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Progenitor identification and SARS-CoV-2 infection in human distal lung organoids
by
Nguyen, Khanh
, Sabatti, Chiara
, Ziraldo, Solongo B.
, van Unen, Vincent
, Ju, Jihang
, Luca, Vincent
, Harbury, Pehr B.
, Desai, Tushar J.
, Flynn, Ryan A.
, Garcia, K. Christopher
, Choi, Shannon S.
, Hart, Daniel J.
, Amieva, Manuel R.
, Terry, Jessica M.
, Salahudeen, Ameen A.
, Belgrader, Phillip
, Margalef-Català, Mar
, Nagendran, Monica
, de la O, Sean M.
, Anchang, Benedict
, Glenn, Jeffrey S.
, Batish, Arpit
, Zheng, Grace X. Y.
, Usui, Tatsuya
, Kuo, Calvin J.
, Rustagi, Arjun
, Wagar, Lisa E.
, Baric, Ralph S.
, Zhu, Junjie
, Blish, Catherine A.
, Santos, António J. M.
, Edwards, Caitlin E.
, Mikkelsen, Tarjei S.
, Davis, Mark M.
in
13/100
/ 13/106
/ 14
/ 14/1
/ 14/19
/ 14/32
/ 38
/ 38/91
/ 45
/ 631/326/596/1578
/ 631/326/596/4130
/ 631/532/2118
/ 82
/ ACE2
/ Alveolar Epithelial Cells - cytology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - virology
/ Alveoli
/ Angiotensin-converting enzyme 2
/ Basal cells
/ Bronchopulmonary infection
/ Cell culture
/ Cell cycle
/ Cell Differentiation
/ Cell Division
/ Clone Cells - cytology
/ Clone Cells - metabolism
/ Clone Cells - virology
/ Coronaviridae
/ Coronaviruses
/ COVID-19
/ COVID-19 - metabolism
/ COVID-19 - pathology
/ COVID-19 - virology
/ Culture
/ Disease transmission
/ Gas exchange
/ Genes
/ Heterogeneity
/ Human cell culture
/ Humanities and Social Sciences
/ Humans
/ In Vitro Techniques
/ Infections
/ Influenza A Virus, H1N1 Subtype - growth & development
/ Influenza A Virus, H1N1 Subtype - physiology
/ Integrin alpha6 - analysis
/ Integrin beta4 - analysis
/ Keratin-5 - analysis
/ Lumens
/ Lung - cytology
/ Lung cancer
/ Lung diseases
/ Lungs
/ Methods
/ Models, Biological
/ multidisciplinary
/ Offspring
/ Organoids
/ Organoids - cytology
/ Organoids - metabolism
/ Organoids - virology
/ Physiological aspects
/ Pneumonia
/ Pneumonia, Viral - metabolism
/ Pneumonia, Viral - pathology
/ Pneumonia, Viral - virology
/ Polarity
/ Respiratory diseases
/ SARS-CoV-2 - growth & development
/ SARS-CoV-2 - physiology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Single-Cell Analysis
/ Stem cells
/ Tissue Culture Techniques
/ TWEAK Receptor - analysis
/ Viral diseases
2020
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Progenitor identification and SARS-CoV-2 infection in human distal lung organoids
by
Nguyen, Khanh
, Sabatti, Chiara
, Ziraldo, Solongo B.
, van Unen, Vincent
, Ju, Jihang
, Luca, Vincent
, Harbury, Pehr B.
, Desai, Tushar J.
, Flynn, Ryan A.
, Garcia, K. Christopher
, Choi, Shannon S.
, Hart, Daniel J.
, Amieva, Manuel R.
, Terry, Jessica M.
, Salahudeen, Ameen A.
, Belgrader, Phillip
, Margalef-Català, Mar
, Nagendran, Monica
, de la O, Sean M.
, Anchang, Benedict
, Glenn, Jeffrey S.
, Batish, Arpit
, Zheng, Grace X. Y.
, Usui, Tatsuya
, Kuo, Calvin J.
, Rustagi, Arjun
, Wagar, Lisa E.
, Baric, Ralph S.
, Zhu, Junjie
, Blish, Catherine A.
, Santos, António J. M.
, Edwards, Caitlin E.
, Mikkelsen, Tarjei S.
, Davis, Mark M.
in
13/100
/ 13/106
/ 14
/ 14/1
/ 14/19
/ 14/32
/ 38
/ 38/91
/ 45
/ 631/326/596/1578
/ 631/326/596/4130
/ 631/532/2118
/ 82
/ ACE2
/ Alveolar Epithelial Cells - cytology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - virology
/ Alveoli
/ Angiotensin-converting enzyme 2
/ Basal cells
/ Bronchopulmonary infection
/ Cell culture
/ Cell cycle
/ Cell Differentiation
/ Cell Division
/ Clone Cells - cytology
/ Clone Cells - metabolism
/ Clone Cells - virology
/ Coronaviridae
/ Coronaviruses
/ COVID-19
/ COVID-19 - metabolism
/ COVID-19 - pathology
/ COVID-19 - virology
/ Culture
/ Disease transmission
/ Gas exchange
/ Genes
/ Heterogeneity
/ Human cell culture
/ Humanities and Social Sciences
/ Humans
/ In Vitro Techniques
/ Infections
/ Influenza A Virus, H1N1 Subtype - growth & development
/ Influenza A Virus, H1N1 Subtype - physiology
/ Integrin alpha6 - analysis
/ Integrin beta4 - analysis
/ Keratin-5 - analysis
/ Lumens
/ Lung - cytology
/ Lung cancer
/ Lung diseases
/ Lungs
/ Methods
/ Models, Biological
/ multidisciplinary
/ Offspring
/ Organoids
/ Organoids - cytology
/ Organoids - metabolism
/ Organoids - virology
/ Physiological aspects
/ Pneumonia
/ Pneumonia, Viral - metabolism
/ Pneumonia, Viral - pathology
/ Pneumonia, Viral - virology
/ Polarity
/ Respiratory diseases
/ SARS-CoV-2 - growth & development
/ SARS-CoV-2 - physiology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Single-Cell Analysis
/ Stem cells
/ Tissue Culture Techniques
/ TWEAK Receptor - analysis
/ Viral diseases
2020
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Do you wish to request the book?
Progenitor identification and SARS-CoV-2 infection in human distal lung organoids
by
Nguyen, Khanh
, Sabatti, Chiara
, Ziraldo, Solongo B.
, van Unen, Vincent
, Ju, Jihang
, Luca, Vincent
, Harbury, Pehr B.
, Desai, Tushar J.
, Flynn, Ryan A.
, Garcia, K. Christopher
, Choi, Shannon S.
, Hart, Daniel J.
, Amieva, Manuel R.
, Terry, Jessica M.
, Salahudeen, Ameen A.
, Belgrader, Phillip
, Margalef-Català, Mar
, Nagendran, Monica
, de la O, Sean M.
, Anchang, Benedict
, Glenn, Jeffrey S.
, Batish, Arpit
, Zheng, Grace X. Y.
, Usui, Tatsuya
, Kuo, Calvin J.
, Rustagi, Arjun
, Wagar, Lisa E.
, Baric, Ralph S.
, Zhu, Junjie
, Blish, Catherine A.
, Santos, António J. M.
, Edwards, Caitlin E.
, Mikkelsen, Tarjei S.
, Davis, Mark M.
in
13/100
/ 13/106
/ 14
/ 14/1
/ 14/19
/ 14/32
/ 38
/ 38/91
/ 45
/ 631/326/596/1578
/ 631/326/596/4130
/ 631/532/2118
/ 82
/ ACE2
/ Alveolar Epithelial Cells - cytology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - virology
/ Alveoli
/ Angiotensin-converting enzyme 2
/ Basal cells
/ Bronchopulmonary infection
/ Cell culture
/ Cell cycle
/ Cell Differentiation
/ Cell Division
/ Clone Cells - cytology
/ Clone Cells - metabolism
/ Clone Cells - virology
/ Coronaviridae
/ Coronaviruses
/ COVID-19
/ COVID-19 - metabolism
/ COVID-19 - pathology
/ COVID-19 - virology
/ Culture
/ Disease transmission
/ Gas exchange
/ Genes
/ Heterogeneity
/ Human cell culture
/ Humanities and Social Sciences
/ Humans
/ In Vitro Techniques
/ Infections
/ Influenza A Virus, H1N1 Subtype - growth & development
/ Influenza A Virus, H1N1 Subtype - physiology
/ Integrin alpha6 - analysis
/ Integrin beta4 - analysis
/ Keratin-5 - analysis
/ Lumens
/ Lung - cytology
/ Lung cancer
/ Lung diseases
/ Lungs
/ Methods
/ Models, Biological
/ multidisciplinary
/ Offspring
/ Organoids
/ Organoids - cytology
/ Organoids - metabolism
/ Organoids - virology
/ Physiological aspects
/ Pneumonia
/ Pneumonia, Viral - metabolism
/ Pneumonia, Viral - pathology
/ Pneumonia, Viral - virology
/ Polarity
/ Respiratory diseases
/ SARS-CoV-2 - growth & development
/ SARS-CoV-2 - physiology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Single-Cell Analysis
/ Stem cells
/ Tissue Culture Techniques
/ TWEAK Receptor - analysis
/ Viral diseases
2020
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Progenitor identification and SARS-CoV-2 infection in human distal lung organoids
Journal Article
Progenitor identification and SARS-CoV-2 infection in human distal lung organoids
2020
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Overview
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate the investigation of pathologies such as interstitial lung disease, cancer and coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we describe the development of a long-term feeder-free, chemically defined culture system for distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5
+
basal cells. AT2 organoids were able to differentiate into AT1 cells, and basal cell organoids developed lumens lined with differentiated club and ciliated cells. Single-cell analysis of
KRT5
+
cells in basal organoids revealed a distinct population of
ITGA6
+
ITGB4
+
mitotic cells, whose offspring further segregated into a
TNFRSF12A
hi
subfraction that comprised about ten per cent of KRT5
+
basal cells. This subpopulation formed clusters within terminal bronchioles and exhibited enriched clonogenic organoid growth activity. We created distal lung organoids with apical-out polarity to present ACE2 on the exposed external surface, facilitating infection of AT2 and basal cultures with SARS-CoV-2 and identifying club cells as a target population. This long-term, feeder-free culture of human distal lung organoids, coupled with single-cell analysis, identifies functional heterogeneity among basal cells and establishes a facile in vitro organoid model of human distal lung infections, including COVID-19-associated pneumonia.
A long-term culture method for organoids derived from single adult human lung cells is used to identify progenitor cells and study SARS-CoV-2 infection.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 14
/ 14/1
/ 14/19
/ 14/32
/ 38
/ 38/91
/ 45
/ 82
/ ACE2
/ Alveolar Epithelial Cells - cytology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - virology
/ Alveoli
/ Angiotensin-converting enzyme 2
/ COVID-19
/ Culture
/ Genes
/ Humanities and Social Sciences
/ Humans
/ Influenza A Virus, H1N1 Subtype - growth & development
/ Influenza A Virus, H1N1 Subtype - physiology
/ Lumens
/ Lungs
/ Methods
/ Pneumonia, Viral - metabolism
/ Pneumonia, Viral - pathology
/ Polarity
/ SARS-CoV-2 - growth & development
/ Science
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