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Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors

View ORCID ProfileKristine M. Abo, Liang Ma, Taylor Matte, Jessie Huang, Konstantinos D. Alysandratos, Rhiannon B. Werder, Aditya Mithal, Mary Lou Beermann, Jonathan Lindstrom-Vautrin, Gustavo Mostoslavsky, Laertis Ikonomou, Darrell N. Kotton, Finn Hawkins, Andrew Wilson, Carlos Villacorta-Martin
doi: https://doi.org/10.1101/2020.06.03.132639
Kristine M. Abo
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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  • ORCID record for Kristine M. Abo
Liang Ma
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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Taylor Matte
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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Jessie Huang
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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Konstantinos D. Alysandratos
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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Rhiannon B. Werder
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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Aditya Mithal
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
3Section of Gastroenterology and Department of Medicine at Boston University and Boston Medical Center, Boston, MA 02118, USA
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Mary Lou Beermann
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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Jonathan Lindstrom-Vautrin
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
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Gustavo Mostoslavsky
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
3Section of Gastroenterology and Department of Medicine at Boston University and Boston Medical Center, Boston, MA 02118, USA
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  • For correspondence: cvmar@bu.edu awilson@bu.edu hawk@bu.edu dkotton@bu.edu laertis@bu.edu gmostosl@bu.edu
Laertis Ikonomou
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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  • For correspondence: cvmar@bu.edu awilson@bu.edu hawk@bu.edu dkotton@bu.edu laertis@bu.edu gmostosl@bu.edu
Darrell N. Kotton
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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  • For correspondence: cvmar@bu.edu awilson@bu.edu hawk@bu.edu dkotton@bu.edu laertis@bu.edu gmostosl@bu.edu
Finn Hawkins
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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  • For correspondence: cvmar@bu.edu awilson@bu.edu hawk@bu.edu dkotton@bu.edu laertis@bu.edu gmostosl@bu.edu
Andrew Wilson
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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  • For correspondence: cvmar@bu.edu awilson@bu.edu hawk@bu.edu dkotton@bu.edu laertis@bu.edu gmostosl@bu.edu
Carlos Villacorta-Martin
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA
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  • For correspondence: cvmar@bu.edu awilson@bu.edu hawk@bu.edu dkotton@bu.edu laertis@bu.edu gmostosl@bu.edu
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Abstract

Development of an anti-SARS-CoV-2 therapeutic is hindered by the lack of physiologically relevant model systems that can recapitulate host-viral interactions in human cell types, specifically the epithelium of the lung. Here, we compare induced pluripotent stem cell (iPSC)-derived alveolar and airway epithelial cells to primary lung epithelial cell controls, focusing on expression levels of genes relevant for COVID-19 disease modeling. iPSC-derived alveolar epithelial type II-like cells (iAT2s) and iPSC-derived airway epithelial lineages express key transcripts associated with lung identity in the majority of cells produced in culture. They express ACE2 and TMPRSS2, transcripts encoding essential host factors required for SARS-CoV-2 infection, in a minor subset of each cell sub-lineage, similar to frequencies observed in primary cells. In order to prepare human culture systems that are amenable to modeling viral infection of both the proximal and distal lung epithelium, we adapt iPSC-derived alveolar and airway epithelial cells to two-dimensional air-liquid interface cultures. These engineered human lung cell systems represent sharable, physiologically relevant platforms for SARS-CoV-2 infection modeling and may therefore expedite the development of an effective pharmacologic intervention for COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 04, 2020.
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Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors
Kristine M. Abo, Liang Ma, Taylor Matte, Jessie Huang, Konstantinos D. Alysandratos, Rhiannon B. Werder, Aditya Mithal, Mary Lou Beermann, Jonathan Lindstrom-Vautrin, Gustavo Mostoslavsky, Laertis Ikonomou, Darrell N. Kotton, Finn Hawkins, Andrew Wilson, Carlos Villacorta-Martin
bioRxiv 2020.06.03.132639; doi: https://doi.org/10.1101/2020.06.03.132639
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Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors
Kristine M. Abo, Liang Ma, Taylor Matte, Jessie Huang, Konstantinos D. Alysandratos, Rhiannon B. Werder, Aditya Mithal, Mary Lou Beermann, Jonathan Lindstrom-Vautrin, Gustavo Mostoslavsky, Laertis Ikonomou, Darrell N. Kotton, Finn Hawkins, Andrew Wilson, Carlos Villacorta-Martin
bioRxiv 2020.06.03.132639; doi: https://doi.org/10.1101/2020.06.03.132639

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