REAGENT or RESOURCE SOURCE IDENTIFIER Biological Samples M. mulatta lung, bone marrow, brain, colon, ileum, jejunum, liver, lung, peripheral blood, spleen, thymus, tonsil, and lymph nodes from various sites Washington National Primate Research Center N/A Human lung tissue from surgical excess University of KwaZulu-Natal IRB Code:BE024/09 Human non-inflamed ileal pinch biopsies Multi-center clinical study, approved by the Institutional Review Board at Boston Children’s Hospital IRB Code:IRB-P00030890 Human nasal lavage University of Massachusetts Medical School N/A Human nasal scraping, polyp scrapings, ethmoid sinus surgical tissue samples Partners HealthCare Institute N/A M. fascicularis lung and granulomatous tissue University of Pittsburgh School of Medicine N/A Antibodies anti-ACE2 human antibody, goat polyclonal R&D Cat#AF933 Bacterial and Virus Strains MHV-68 Adler et al., 2000 N/A Mycobacterium Tuberculosis, Modified Erdman Strain Martin et al., 2017 N/A Chemicals, Peptides, and Recombinant Proteins 2-Mercaptoethanol Sigma Cat#M3148-25ML RLT Buffer QIAGEN Cat#79216 dNTP New England BioLabs Cat#N0447L RNase Inhibitor Fisher Scientific Cat#AM2696 Maxima RNaseH-minus RT Enzyme Fisher Scientific Cat#EP0753 MgCl2 Sigma Cat#63069-100ML Betaine Sigma Cat#B0300-5VL AMPure RNAClean XP RNA-SPRI beads Beckman Coulter Cat#A63987 AMPure XP SPRI beads Beckman Coulter Cat#A63881 Guanidinium thiocyanate Sigma Cat#AM9422 Sarkosyl Sigma Cat#L7414 Exonuclease I New England BioLabs Cat#M0293S Klenow Fragment New England BioLabs Cat#M0212L DNase I Roche Cat#10104159001 Collagenase IV Life Technologies Cat#17104019 Collagenase D Roche Cat#11088858001 Liberase TM Roche Cat#5401119001 TrypLE Thermo Fisher Cat#12604013 ACK Buffer Thermo Fisher Cat#A1049201 IFN-α Biolegend Cat#752802 Dispase II Thermo Fisher Cat#17105041 Elastase Worthington Biochem Cat#LS002292 Pneumacult-Ex serum-free media StemCell Technologies, Inc. Cat#05040 IL-4, human Biolegend Cat#574002 IL17A, human Biolegend Cat#570502 IFNγ, human Biolegend Cat#570202 IFNγ, mouse Peprotech Cat#315-05 IFNα, human Biolegend Cat#592702 IFNα, mouse Biolegend Cat#752802 IFNβ, mouse R&D Systems Cat#8234-MB-010 Critical Commercial Assays Nextera XT DNA Library Preparation Kit Illumina Cat#FC-131-1096 High Sensitivity D5000 ScreenTape Agilent Cat#5067-5592 Qubit dsDNA High-Sensitivity kit ThermoFisher Cat#Q32854 NextSeq 500/550 High Output v2 (75 cycles) Illumina Cat#FC-404-2005 NovaSeq 6000 S2 (100 cycles) Illumina Cat#20012862 Kapa HiFi HotStart ReadyMix Kapa Biosystems Cat#KK2602 MACOSKO-2011-10 mRNA Capture Beads ChemGenes Cat#NC0927472 Tumor Dissociation Kit, Human Miltenyi Biotec Cat#130-095-929 Chromium Single Cell 3′ v2 10X Genomics Cat#120237 Deposited Data scRNA-seq Processed Data This paper https://singlecell.broadinstitute.org/single_cell?scpbr=the-alexandria-project scRNA-seq Processed Data This paper https://drive.google.com/drive/folders/1bxCIqNeZ7wLuVOT16gphwj98_cc9KhrV?usp=sharing scRNA-seq Processed Data This paper https://chanzuckerberg.github.io/cellxgene/posts/cellxgene_cziscience_com scRNA-seq Processed Data This paper https://singlecell.broadinstitute.org/single_cell/covid19 scRNA-seq Processed Data (all species) and FASTQ files (for NHP and murine datasets) This paper GEO: GSE148829 scRNA-seq data from human nasal mucosa Ordovas-Montanes et al., 2018 https://singlecell.broadinstitute.org/single_cell/study/SCP253/allergic-inflammatory-memory-in-human-respiratory-epithelial-progenitor-cells Human reference genome NCBI build 38 (GRCh38) Genome Reference Consortium http://www.ncbi.nlm.nih.gov/projects/genome/assembly/grc/human/ Human reference genome NCBI build 19 Genome Reference Consortium http://www.ncbi.nlm.nih.gov/projects/genome/assembly/grc/human/ Mouse reference genome NCBI build 10 Genome Reference Consortium http://www.ncbi.nlm.nih.gov/projects/genome/assembly/grc/mouse/ Macaca mulatta reference genome assembly 8.0.1, annotation 102 NCBI Eukaryotic Genome Annotation Pipeline https://www.ncbi.nlm.nih.gov/genome/annotation_euk/Macaca_mulatta/102/ Macaca fascicularis reference genome assembly 5, annotation 101 NCBI Eukaryotic Genome Annotation Pipeline https://www.ncbi.nlm.nih.gov/genome/annotation_euk/Macaca_fascicularis/101/ Interferome Database Rusinova et al., 2013 http://www.interferome.org/ RNA-seq from human lung explants ± ex vivo IAV infection Matos et al., 2019 GEO: GSE135069 RNA-seq from human nasal epithelial cells Giovannini-Chami et al., 2012 GEO: GSE19190, GSE22147 Experimental Models: Cell Lines Human: Passage 4 BEAS-2B ATCC CRL-9609 Experimental Models: Organisms/Strains Mouse: C57BL/6J The Jackson Laboratory Cat#000664 Mouse: C57BL/6, IFNγR−/− B6.129S7-Ifngr1tm1Agt/J The Jackson Laboratory Cat#003288 Oligonucleotides SMART-seq2 2 3′ Oligo-dT Primer: /5Biosg/AAG CAG TGG TAT CAA CGC AGA GTA CTT TTT TTT TTT TTT TTT TTT TTT TTT TTT TVN Integrated DNA Technologies N/A SMART-seq2 5′ TSO: AAG CAG TGG TAT CAA CGC AGA GTA CAT rGrGrG Integrated DNA Technologies N/A SMART-seq2 and Seq-Well ISPCR:AAG CAG TGG TAT CAA CGC AGA GT Integrated DNA Technologies N/A Custom Read 1 Primer: GCC TGT CCG CGG AAG CAG TGG TAT CAA CGC AGA GTA C Integrated DNA Technologies N/A Seq-Well 5′ TSO: AAG CAG TGG TAT CAA CGC AGA GTG AAT rGrGrG Integrated DNA Technologies N/A Seq-Well Custom P5-SMART PCR hybrid oligo: AAT GAT ACG GCG ACC ACC GAG ATC TAC ACG CCT GTC CGC GGA AGC AGT GGT ATC AAC GCA GAG TAC Integrated DNA Technologies N/A Seq-Well dN-SMRT oligo: AAG CAG TGG TAT CAA CGC AGA GTG ANN NGG NNN B Integrated DNA Technologies N/A Software and Algorithms R R Core Team https://www.r-project.org R package – Seurat v2.3.4 and v3.1.0 Github https://github.com/satijalab/seurat Scanpy Wolf et al., 2018 https://github.com/theislab/scanpy R package – SCDE Bioconductor http://bioconductor.org/packages/scde/ Prism 6 GraphPad Software https://www.graphpad.com/scientific-software/prism/ STAR Github https://github.com/alexdobin/STAR Uniform Manifold Approximation and Projection Github https://github.com/lmcinnes/umap Rtsne CRAN https://cran.r-project.org/web/packages/Rtsne/