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Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction.

dc.contributor.author Katsura, Hiroaki
dc.contributor.author Sontake, Vishwaraj
dc.contributor.author Tata, Aleksandra
dc.contributor.author Kobayashi, Yoshihiko
dc.contributor.author Edwards, Caitlin E
dc.contributor.author Heaton, Brook E
dc.contributor.author Konkimalla, Arvind
dc.contributor.author Asakura, Takanori
dc.contributor.author Mikami, Yu
dc.contributor.author Fritch, Ethan J
dc.contributor.author Lee, Patty J
dc.contributor.author Heaton, Nicholas S
dc.contributor.author Boucher, Richard C
dc.contributor.author Randell, Scott H
dc.contributor.author Baric, Ralph S
dc.contributor.author Tata, Purushothama Rao
dc.date.accessioned 2020-11-19T19:02:53Z
dc.date.available 2020-11-19T19:02:53Z
dc.date.issued 2020-10-21
dc.identifier S1934-5909(20)30499-9
dc.identifier.issn 1934-5909
dc.identifier.issn 1875-9777
dc.identifier.uri https://hdl.handle.net/10161/21706
dc.description.abstract Coronavirus infection causes diffuse alveolar damage leading to acute respiratory distress syndrome. The absence of ex vivo models of human alveolar epithelium is hindering an understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here, we report a feeder-free, scalable, chemically defined, and modular alveolosphere culture system for the propagation and differentiation of human alveolar type 2 cells/pneumocytes derived from primary lung tissue. Cultured pneumocytes express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor angiotensin-converting enzyme receptor type-2 (ACE2) and can be infected with virus. Transcriptome and histological analysis of infected alveolospheres mirror features of COVID-19 lungs, including emergence of interferon (IFN)-mediated inflammatory responses, loss of surfactant proteins, and apoptosis. Treatment of alveolospheres with IFNs recapitulates features of virus infection, including cell death. In contrast, alveolospheres pretreated with low-dose IFNs show a reduction in viral replication, suggesting the prophylactic effectiveness of IFNs against SARS-CoV-2. Human stem cell-based alveolospheres, thus, provide novel insights into COVID-19 pathogenesis and can serve as a model for understanding human respiratory diseases.
dc.language eng
dc.publisher Elsevier BV
dc.relation.ispartof Cell stem cell
dc.relation.isversionof 10.1016/j.stem.2020.10.005
dc.subject ACE2
dc.subject ARDS
dc.subject SARS-CoV-2
dc.subject cytokine storm
dc.subject interferons
dc.subject organoids
dc.subject pneumocytes
dc.subject protease
dc.subject respiratory cells
dc.subject surfactants
dc.title Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction.
dc.type Journal article
duke.contributor.id Heaton, Brook E|0693847
duke.contributor.id Lee, Patty J|0959308
duke.contributor.id Heaton, Nicholas S|0689635
duke.contributor.id Tata, Purushothama Rao|0719951
dc.date.updated 2020-11-19T19:02:49Z
pubs.organisational-group School of Medicine
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Cell Biology
pubs.organisational-group Duke
pubs.organisational-group Institutes and Centers
pubs.organisational-group Basic Science Departments
pubs.organisational-group Medicine, Pulmonary, Allergy, and Critical Care Medicine
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
duke.contributor.orcid Tata, Purushothama Rao|0000-0003-4837-0337


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