Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells

E. A. Rosado-Olivieri, B. Razooky, J. Le Pen, R. De Santis, D. Barrows, Z. Sabry, H. H. Hoffmann, J. Park, T. S. Carroll, J. T. Poirier, C. M. Rice, A. H. Brivanlou

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1107-1122
Number of pages16
JournalStem Cell Reports
Issue number5
StatePublished - May 9 2023


  • BMP signaling
  • COVID-19
  • SARS-CoV-2
  • endemic coronaviruses
  • fetal lung
  • lung buds
  • lung development
  • lung differentiation
  • lung organoids
  • micropatterned hESCs

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology


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