02127nas a2200397   4500000000100000008004100001260001500042653001800057653001300075653001500088653002600103653001500129653001400144653002100158653002500179653001900204653002500223100002600248700001500274700001400289700001700303700001500320700001300335700002000348700001200368700001800380700001800398700001500416700002000431245010100451856007200552300001400624490000700638520107000645022001401715       2023                            d  c2023-05-0910aBMP signaling10aCOVID-1910aSARS-CoV-210aendemic coronaviruses10afetal lung10alung buds10alung development10alung differentiation10alung organoids10amicropatterned hESCs1 aE. A. Rosado-Olivieri1 aB. Razooky1 aJ. Le Pen1 aR. De Santis1 aD. Barrows1 aZ. Sabry1 aH. -H. Hoffmann1 aJ. Park1 aT. S. Carroll1 aJ. T. Poirier1 aC. M. Rice1 aA. H. Brivanlou00aOrganotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells  uhttps://www.sciencedirect.com/science/article/pii/S2213671123001030  a1107-11220 v183 aAlthough 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.  a2213-6711