Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19.

BioRxiv : the Preprint Server for Biology
Courtney TindleSoumita Das

Abstract

SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection, whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines. Human lung organoids with mixed proximodistal epithelia are createdProximal airway cells are critical for viral infe...Continue Reading

Citations

Jan 13, 2021·Cells·Rishi Man ChughSubhrajit Saha
Jan 15, 2021·Clinical Microbiology Reviews·Aleksandra SynowiecKrzysztof Pyrc
Jun 5, 2021·Nature Communications·Malina A BakowskiThomas F Rogers
May 25, 2021·Current Opinion in Pharmacology·Sonia YouhannaVolker M Lauschke
May 24, 2021·Frontiers in Medicine·Mirjam KienerMarianna Kruithof-de Julio

Datasets Mentioned

BETA
GSE155241

Methods Mentioned

BETA
single-cell sequencing
biopsies
RNA Seq
confocal microscopy
bronchoalveolar lavage

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