TY - JOUR
KW - BMP signaling
KW - COVID-19
KW - SARS-CoV-2
KW - endemic coronaviruses
KW - fetal lung
KW - lung buds
KW - lung development
KW - lung differentiation
KW - lung organoids
KW - micropatterned hESCs
AU - E. A. Rosado-Olivieri
AU - B. Razooky
AU - J. Le Pen
AU - R. De Santis
AU - D. Barrows
AU - Z. Sabry
AU - H. -H. Hoffmann
AU - J. Park
AU - T. S. Carroll
AU - J. T. Poirier
AU - C. M. Rice
AU - A. H. Brivanlou
AB - 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.
BT - Stem Cell Reports
DA - 2023-05-09
DO - 10.1016/j.stemcr.2023.03.015
IS - 5
N2 - 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.
PY - 2023
SP - 1107
EP - 1122
T2 - Stem Cell Reports
TI - Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells
UR - https://www.sciencedirect.com/science/article/pii/S2213671123001030
VL - 18
Y2 - 2023-09-15
SN - 2213-6711
ER -