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


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.





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Publication Info

Katsura, Hiroaki, Vishwaraj Sontake, Aleksandra Tata, Yoshihiko Kobayashi, Caitlin E Edwards, Brook E Heaton, Arvind Konkimalla, Takanori Asakura, et al. (2020). Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction. Cell stem cell. 10.1016/j.stem.2020.10.005 Retrieved from

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Aleksandra Tata

Assistant Research Professor of Cell Biology

Brook Heaton

Assistant Research Professor of Molecular Genetics and Microbiology

Nicholas Scott Heaton

Associate Professor of Molecular Genetics and Microbiology

Our research group is primarily interested in the study of respiratory RNA viruses.  We have published work on viruses of the families: orthomyxoviridae, paramyxoviridae, and coronaviridae.  The research in our laboratory is predominantly focused understanding the mechanisms of viral pathogenesis with the ultimate goal of developing new therapies that can be used to combat both current and future viral diseases.


Purushothama Rao Tata

Associate Professor of Cell Biology

Lung regeneration
Lung stem cells
Cell plasticity
Organoid models
Lung Fibrosis
Single Cell Biology

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