Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells.
Stem Cell Reports
; 18(5): 1107-1122, 2023 05 09.
Article
in En
| MEDLINE
| ID: mdl-37084725
ABSTRACT
Although lung disease is the primary clinical outcome in COVID-19 patients, how SARS-CoV-2 induces lung pathology remains elusive. Here we describe a high-throughput platform to generate self-organizing and commensurate human lung buds derived from hESCs cultured on micropatterned substrates. Lung buds resemble human fetal lungs and display proximodistal patterning of alveolar and airway tissue directed by KGF. These lung buds are susceptible to infection by SARS-CoV-2 and endemic coronaviruses and can be used to track cell type-specific cytopathic effects in hundreds of lung buds in parallel. Transcriptomic comparisons of infected lung buds and postmortem tissue of COVID-19 patients identified an induction of BMP signaling pathway. BMP activity renders lung cells more susceptible to SARS-CoV-2 infection and its pharmacological inhibition impairs infection by this virus. These data highlight the rapid and scalable access to disease-relevant tissue using lung buds that recapitulate key features of human lung morphogenesis and viral infection biology.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
COVID-19
Limits:
Humans
Language:
En
Journal:
Stem Cell Reports
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos