REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
APC Mouse IgG1, κ isotype control (FC) antibody	Biolegend	400121
APC Mouse IgG2a, kappa isotype control antibody	Biolegend	400219
donkey α-goat AF488	Invitrogen	A11055
donkey α-goat AF568	Invitrogen	A11057
donkey α-goat AF647	Invitrogen	A21447
donkey α-mouse AF488	Invitrogen	A21202
donkey α-mouse AF568	Invitrogen	A10037
donkey α-mouse AF647	Invitrogen	A31571
donkey α-rabbit AF488	Invitrogen	A11008
donkey α-rabbit AF568	Invitrogen	A10042
donkey α-rabbit AF647	Invitrogen	A31573
goat α-chicken AF488	Invitrogen	A11039
Mouse monoclonal anti-CD324(E-CAD)	BD Biosciences	610181
Mouse monoclonal anti-acetylated Tubulin (TUBA)	Sigma	T7451
Mouse monoclonal anti-ACE2	Proteintech	66699-1-AP
Mouse monoclonal anti-dsRNA	Absolute Antibodies	Ab01299-2.0
Mouse monoclonal anti-SARS/SARS-CoV-2 Nucleocapsid	Invitrogen	MA1-7404
Rabbit monoclonal anti-Sox9	Cell Signaling Technologies	82630T
Mouse monoclonal APC anti-human CD184 (CXCR4)	Biolegend	306509
Mouse Monoclonal PE anti-human CD117 (c-kit)	Biolegend	313203
PE Mouse IgG1, kappa isotype control antibody	Biolegend	400111
PE Mouse IgG2a, κ isotype control antibody	Biolegend	400211
Goat polyclonal anti-ACE2	R&D Systems	AF933
Rabbit polyclonal anti-ACE2	Proteintech	#21115-1-AP
Chicken polyclonal anti-GFP	abcam	ab13970
Rabbit polyclonal anti-NKX2.1	Seven Hills Bioreagents	WMAB-1231
Goat polyclonal anti-TMPRSS2	Novus Biologicals	#NBP1-20984
Bacterial and Virus Strains
SARS-CoV-2/human/USA/CA-UCSF-0001C/2020	UCSF Clinical Specimen	N/A
USA-WA1/2020, NR-52281 isolate	BEI Resources	N/A
G-complemented G∗ΔG-GFP rVSV	Kerafast	EH1024-PM
Biological Samples
Donated lung tissue from transplant recipients	Laboratory of David J. Erle	N/A
Chemicals, Peptides, and Recombinant Proteins
8-Br-cAMP	Sigma-Aldrich Inc	B5386
Accutase	Stemcell Tech	7922
Activin A	R&D Systems	338AC010
All-trans retinoic acid	Stemcell Tech	72264
Ascorbic acid	Sigma-Aldrich Inc	A4034
BMP4	Stemcell Tech	78211.2
Camostat mesilate	Selleck Chem (FDA-Approved Library)	N/A
cAMP	Sigma-Aldrich Inc	D0627
Cas9-NLS purified protein	QB3 MacroLab	N/A
CHIR99021	Stem-RD	CHIR
Collagen, Type IV, Human Placenta	Sigma-Aldrich Inc	234154
DAPI	Thermo Fisher Scientific	D1306
Dexamethasone	Sigma-Aldrich Inc	D4902
DHT	Sigma-Aldrich Inc	D-073
Dispase	Corning	354235
Dutasteride	Selleck Chemicals LLC	S1202
0.5M EDTA, pH 8.0	Thermo Fisher Scientific	15575020
FGF10	Stemcell Tech	78037.2
FGF4	Stemcell Tech	78103.2
FGF7	Stemcell Tech	78046.1
Fibronectin	Corning	DLW354008
Finasteride	Selleck Chemicals LLC	S1197
Guanabenz acetate	Selleck Chem (FDA-Approved Library)	N/A
IBMX	Sigma-Aldrich Inc	I5879
Ketoconazole	Selleck Chemicals LLC	S1353
Laminin	Corning	354232
LDN193189	Stemgent	#04-0074-02
Library of FDa-approved drugs (1443 compounds)	Selleck Chem	L1300
Monothioglycerol	Sigma-Aldrich Inc	M6145
Paraformaldehyde	Thermo Fisher Scientific	AAJ19943K2
Paraformaldehyde, 4% solution	SCBT	sc-281692
Poly-L-ornithine hydrobromide	Sigma	P3655
SAG	Stemcell Tech	73412
SARS-CoV-2 (2019-nCoV) Spike RBD-Fc Recombinant Protein	Sino Biological	40592-V02H
SB431542	PeproTech	3014193
Sotagliflozin	Selleck Chem (FDA-Approved Library)	N/A
0.05% Trypsin/0.53mM EDTA	Corning	25-051-Cl
XAV939	R&D	3746
Critical Commercial Assays
PowerUp™ SYBR™ Green Master Mix	Thermo Fisher Scientific	A25743
Cell Staining Buffer	Biolegend	420201
Chromium Next GEM Single Cell 3¢ Kit v3.1	10X Genomics	1000121
eBioscience™ Permeabilization Buffer (10X)	Invitrogen	00-8333-56
Gene Knockout Kit v2 - AR	Synthego	N/A
Gene Knockout Kit v2 - SRD5A1	Synthego	N/A
Lipofectamine 3000 Transfection Kit (0.1 mL)	Fisher Scientific	L3000001
Lipofectamine Cas9 Plus Reagent (ThermoFisher Scientific, USA)	Fisher Scientific	CMAX00008
Lipofectamine CRISPRMAX transfection reagent	Fisher Scientific	CMAX00008
P3 Primary Cell 96-Well Kit	Lonza	V4SP-3096
QuantSeq FWD Kit (with UMI module)	Lexogen	#015
Quick-RNA 96 Kit (Zymo)	Zymo Research	R1052
RNA/DNA/Protein Purification Plus Kit (Norgen Biotek, Thorold, ON, Canada)	Norgen Biotek	47700
SuperScript III First-Strand Synthesis System	ThermoFisher Scientific	18080051
TotalSeq HTO antibodies	Biolegend	#394601-394629
Deposited Data
Deidentified aggregate patient data from Yale New Haven Hospital	available upon request	N/A
Bulk and single cell RNA sequencing data on hESC-derived lung organoids	GEO	GEO: GSE161264
UK Biobank patient data	available upon request	N/A
Experimental Models: Cell Lines
Human embryonic stem cells, H1	WiCell	WA01
Human embryonic stem cells, H9	WiCell	WA09
Human Pulmonary Alveolar Epithelial Cells	Sciencell	#3200
Calu-3 (ATCC® HTB-55™)	ATCC	ATCC® HTB-55™
VERO C1008 [Vero 76, clone E6, Vero E6]	ATCC	CRL-1586
Recombinant DNA
Plasmid: PLVX H2B Cherry	Laboratory of Deepak Lamba	N/A
Mammalian expression plasmid for SARS-CoV-2 surface glycoprotein (Spike) for VSV pseudotyping (Ginkgo Bioworks)	addgene	pGBW-m4137382
Software and Algorithms
GE Developer Toolbox v1.9.1	GE Healthcare	https://www.gehealthcare.com/
ImageJ (FIJI)	NIH	https://imagej.net/Fiji
iPAGE gene ontology analysis	Goodarzi et al. (2009)	https://tavazoielab.c2b2.columbia.edu/iPAGE/
R package: cutadapt v2.10	CRAN package repository	https://cran.r-project.org/web/packages/
R package: DESeq2 v1.30.0	CRAN package repository	https://cran.r-project.org/web/packages/
R package: DropletUtils v1.10.0	CRAN package repository	https://cran.r-project.org/web/packages/
R package: HTSeq v0.12.4	CRAN package repository	https://cran.r-project.org/web/packages/
R package: kb-python v0.24.4	CRAN package repository	https://cran.r-project.org/web/packages/
R package: Seurat v3.2.2	CRAN package repository	https://cran.r-project.org/web/packages/
R package: STAR v2.7.6a	CRAN package repository	https://cran.r-project.org/web/packages/
R package: umi_tools v1.1.0	CRAN package repository	https://cran.r-project.org/web/packages/
R v3.6.3	The R Project for Statistical Computing	https://www.r-project.org/
SEA computational tool	Keiser et al., 2007	http://sea.bkslab.org/
STRING v11 protein-protein interaction (PPI) network analysis	Szklarczyk et al. Nucleic acids research 47.D1 (2018): D607-D613.2	https://string-db.org/
Other
AR ChIP-seq dataset generated in LNCaP cells	Tran et al., 2020	N/A
Previously published single cell RNA sequencing datasets	Madissoon et al., 2019; Smillie et al., 2019; Wang et al., 2020	N/A
Previously published transcriptomics data on hESC-derived cells	Tsai et al., 2020	N/A
SMILES for each drug in FDA-approved library	Selleckchem	https://www.selleckchem.com/screening/fda-approved-drug-library.html
ZINC15 library	Sterling and Irwin, 2015	https://zinc15.docking.org/