ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/074/SRR13094674/SRR13094674_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/076/SRR13094676/SRR13094676_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/075/SRR13094675/SRR13094675_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/075/SRR13094675/SRR13094675_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/077/SRR13094677/SRR13094677_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/074/SRR13094674/SRR13094674_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/077/SRR13094677/SRR13094677_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/076/SRR13094676/SRR13094676_1.fastq.gzprimaryOK200GenomicsSingle Cell Discoverieshttps://www.ebi.ac.uk/ena/browser/view/PRJNA679844Homo sapiensSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), may result in acute respiratory distress syndrome (ARDS), multi-organ failure and death. The alveolar epithelium is a major target of the virus, but representative models to study virus host interactions in more detail are currently lacking. Here, we describe a human 2D air-liquid interface culture system which was characterized by confocal-, electron-microscopy and single cell mRNA expression analysis. In this model, alveolar cells, but also basal cells and rare neuroendocrine cells, are grown from 3D self-renewing lung bud tip organoids. These cultures were readily infected by SARS-CoV-2 with mainly surfactant protein C-positive ATII-like cells being targeted. Consequently, significant viral titers were detected and mRNA expression analysis revealed induction of type I/III interferon response program. Treatment of these cultures with a low dose of interferon lambda dramatically reduced viral replication. Hence, these cultures represent an experimental model for SARS-CoV-2 infection and can be applied for drug screens. Overall design: We have setup a bronchioalveolar model for studying COVID-19. scRNAseq was performed to characterize the model on air-liquid interface bronchioalveolar cells not infected with SARS-CoV-2.xref:PubMed:33283287ENATaf[[II]]250, Taf200, dTAF[[II]]230, TAF[[II]]250, d230, dTAF[[II]]250, TAF[[II]]230, TFIID TAF250, cel, cell, TAF200, l(3)84Ab, RNA-seq, dTAFII250, Taf1p, TAF[II]250, BG:DS00004.13, TAFII-250, CG17603, TAF250/230, TAF[[II]], EfW1, Cell, retina autoimmune disease, dTAF230, dTAF250, dmTAF[[II]]230, TAFII250, DmelCG17603, Taf250, dmTAF1, AIR, SR3-5, Taf230, autoimmune disease of retina, p230, TAF[[II]]250/230, TFIID, Whole Transcriptome Shotgun Sequencing, Cell., liquid, TAF, TAF230, TAF250, TAF1Taf[[II]]250, Taf200, dTAF[[II]]230, TAF[[II]]250, d230, dTAF[[II]]250, TAF[[II]]230, TFIID TAF250, cel, cell, TAF200, l(3)84Ab, RNA-seq, dTAFII250, Taf1p, TAF[II]250, BG:DS00004.13, TAFII-250, CG17603, TAF250/230, TAF[[II]], EfW1, Cell, retina autoimmune disease, dTAF230, dTAF250, dmTAF[[II]]230, TAFII250, DmelCG17603, Taf250, dmTAF1, AIR, SR3-5, Taf230, autoimmune disease of retina, p230, TAF[[II]]250/230, TFIID, Whole Transcriptome Shotgun Sequencing, Cell., liquid, TAF, TAF230, TAF250, TAF1falseSingle-cell RNA-seq of air-liquid interface bronchioalveolar cellsSingle-cell RNA-seq of air-liquid interface bronchioalveolar cells2025-09-242021-01-31PRJNA679844GSE161934960633283287