KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rat Anti-Mouse CD16 / CD32 Monoclonal Antibody	BD Biosciences	Clone 2.4G2, Cat# 553142, RRID:AB_394657
Human TruStain FcX	Biolegend	Cat# 422301, RRID:AB_2847850
Rat Anti-Mouse CD45 Monoclonal Antibody, APC	BD Biosciences	Clone 30-F11, Cat# 559864, RRID:AB_398672
Rat Anti-Mouse CD31 Monoclonal Antibody, APC	BD Biosciences	Clone MEC 13.3, Cat# 561814, RRID:AB_10893351
Rat Anti-Mouse CD11b Monoclonal Antibody, APC	BD Biosciences	Clone M1/70, Cat# 561690, RRID:AB_10897015
Rat Anti-Mouse TER-119 Monoclonal Antibody, APC	BD Biosciences	Clone TER-119, Cat# 561033, RRID:AB_10584336
Rat Anti-Mouse CD45, FITC	Invitrogen	Clone 30-F11, Cat# 11-0451-82, RRID:AB_465050
Rat Anti-Mouse CD31, FITC	Invitrogen	Clone 390, Cat# 11-0311-82, RRID:AB_465012
Rat Anti-Mouse CD11b, FITC	Invitrogen	Clone M1/70, Cat# 11-0112-82, RRID:AB_464935
Hamster Anti-Mouse CD11c, FITC	Biolegend	Clone N418, Cat# 117305, RRID:AB_313774
Rat Anti-Mouse F4/80, FITC	Invitrogen	Clone BM8, Cat# 11-4801-82, RRID:AB_2637191
Rat Anti-Mouse TER-119/Erythroid Cells, FITC	Biolegend	Clone TER-119, Cat# 116206, RRID:AB_313707
Mouse Anti-Mouse CD109, AF647	Santa Cruz Biotechnology	Clone C-9, Cat# sc-271085 AF647, RRID:AB_2847851
Rat Anti-Mouse CD45, APC	Invitrogen	Clone 30-F11, Cat# 17-0451-82, RRID:AB_469392
Rat Anti-Mouse CD31, APC	Invitrogen	Clone 390, Cat# 17-0311-82, RRID:AB_657735
Rat Anti-Mouse CD11b, APC	Invitrogen	Clone M1/70, Cat# 17-0112-82, RRID:AB_469343
Hamster Anti-Mouse CD11c, APC	Biolegend	Clone N418, Cat# 117310, RRID:AB_313779
Rat Anti-Mouse F4/80, APC	Invitrogen	Clone BM8, Cat# 17-4801-82, RRID:AB_2784648
Rat Anti-Mouse TER-119, APC	Invitrogen	Clone TER-119, Cat# 17-5921-82, RRID:AB_469473
Rat Anti-Mouse CD326 (EpCAM), PE	Invitrogen	Clone G8.8, Cat# 12-5791-82, RRID:AB_953615
Mouse Anti-Mouse TIGIT, BV421	Biolegend	Clone 1G9, Cat# 142111, RRID:AB_2687311
Mouse Anti-Human CD45, FITC	Invitrogen	Clone HI30, Cat# 11-0459-42, RRID:AB_10852703
Mouse Anti-Human CD31, FITC	Biolegend	Clone WM59, Cat# 303104, RRID:AB_314330
Mouse Anti-Human CD11b, FITC	Biolegend	Clone ICRF44, Cat# 301330, RRID:AB_2561703
Mouse Anti-Human CD11c, FITC	Biolegend	Clone 3.9, Cat# 301604, RRID:AB_314174
Mouse Anti-Mouse H-2Kd, FITC	Biolegend	Clone SF1-1.1, Cat# 116606, RRID:AB_313741
Mouse Anti-Human CD326 (EpCAM), PE/Cy7	Biolegend	Clone 9C4, Cat# 324222, RRID:AB_2561506
Mouse Anti-Human CD49b (Integrin α2), APC	Biolegend	Clone P1E6-C5, Cat# 359309, RRID:AB_2564198
Mouse Anti-Claudin 2	Invitrogen	Clone 12H12, Cat# 32-5600, RRID:AB_2533085
Rabbit Anti-Claudin 4	Invitrogen	Clone ZMD.306, Cat# 36-4800, RRID:AB_2533262
Rabbit Anti-Lysozyme	DAKO	Clone EC3.2.1.17, Cat# A0099, RRID:AB_2341230
Rabbit Anti-Prosurfactant Protein C	Millipore	Cat# AB3786, RRID:AB_91588
Rabbit Anti-Integrin α2	Abcam	Clone EPR17338, Cat# 181548, RRID:AB_2847852
Rabbit Anti-RFP	Rockland	Cat# 600-401-379, RRID:AB_2209751
Bacterial and Virus Strains
Ad5mSPC	Viral Vector Core, University of Iowa	N/A
Biological Samples
N/A
Chemicals, Peptides, and Recombinant Proteins
DAPI	Sigma-Aldrich	D9542-1MG
YOPRO-1	Invitrogen	Y3603
Advanced DMEM/F12	Gibco	12634028
DMEM	Gibco	10313039
B27 Supplement	Gibco	17504044
FGF-7 (KGF)	PeproTech	100-19
FGF-10	PeproTech	100-26-50ug
Noggin	PeproTech	120-10C-50ug
EGF	PeproTech	AF-100-15-100ug
N-Acetylcysteine	Sigma-Aldrich	A9165-5G
Nicotinamide	Sigma-Aldrich	N0636-100G
SB431542	SelleckChem	S1067
CHIR99021	Sigma-Aldrich	SML1046-5MG
HEPES	Gibco	15630080
Penicillin/Streptomycin	Gibco	15140163
L/glutamine	Gibco	35050061
Y-27632	SelleckChem	S1049
D-Luciferin	Perkin Elmer	122799
S-MEM	Gibco	11380037
Dispase II	Gibco	17105-041
Collagenase Type IV	Thermo Fisher Scientific	17104019
DNase I	Sigma-Aldritch	69182-3
Gentamicin	Gibco	15750-060
ACK	Thermo Fisher Scientific; Lonza	A1049201; 10-548E
TCL Buffer	Qiagen	1031576
Maxima Reverse Transcriptase	Thermo Fisher Scientific	EP0752
Digitonin	Promega	G9441
Illumina Tagment DNA Enzyme	Illumina	15027865
BamBanker Cell Freezing Medium	Lymphotec	302-14681
Matrigel	Corning	CB-40230C
Penicillin-Streptomycin	Gibco	15140163
Corning Dispase	Corning	354235
TrypLE	Gibco	12604013
Cisplatin	EMD-Millipore	232120
Shandon Zinc Formal-Fixx	Thermo Scientific	6764255
Vectashield with DAPI	Vector Labs	H-1200
ImmPACT DAB Peroxidase (HRP) Substrate	Vector Labs	SK-4105
Critical Commercial Assays
RNAscope® 2.5 HD Detection Reagents-RED	ACDBio	322360
DapB ISH Probe	ACDBio	310043
Ppib Mouse ISH Probe	ACDBio	313911
Slc4a11 Mouse ISH Probe	ACDBio	559521
Tigit Mouse ISH Probe	ACDBio	319751
PPIB Human ISH Probe	ACDBio	313901
SLC4A11 Human ISH Probe	ACDBio	583931
Lung Dissociation Kit	Miltenyi Biotech	130-095-927
Tumor Dissociation Kit	Miltenyi Biotech	130-095-929
Agencourt RNAClean XP beads	Beckman Coulter	A63881
KAPA HiFi HotStart ReadyMix	KAPA Biosystems	KK2601
Agencourt AMPure XP beads	Beckman Coulter	A63881
Nextera XT Library Prep kit	Illumina	FC-131-1096
GenomePlex Single Cell Whole Genome Amplification Kit	Sigma	254-457-8
Qiagen MinElute PCR Purification Kit	Qiagen	28004
Chromium Single Cell ATAC Library Kit v1 chemistry	10x Genomics	PN-1000083
Qiagen RNeasy Plus Mini kit	Qiagen	74136
Qiagen RNeasy Plus Micro kit	Qiagen	74034
SuperScript VILO cDNA synthesis kit	Invitrogen	11754050
PrimeScript RT Reagent kit	Takara	RR037B
Powerup SYBR mix	Applied Biosystems	A25778
ImmPRESS HRP Anti-Rabbit IgG (Peroxidase) Polymer Detection Kit	Vector Labs	MP-7401-50
Mouse-on-Mouse ImmPRESS HRP (Peroxidase) Polymer Kit	Vector Labs	MP-2400
Deposited Data
Single cell RNAseq (SmatrtSeq2,10X, DNA, ATAC) & Bulk ATAC	This paper	GEO: GSE152607
Human single cell lung adeno tumors	Zilionis et al.	GEO: GSE127465
Human single cell lung adeno tumors	Lambrechts et al.	E-MTAB-6653, E-MTAB-6653
Human single cell lung adeno tumors	Laughney et al.	GEO: GSE123903
TCGA LUAD	MC3
TCGA PanCan	LinkedOmics	http://www.linkedomics.org/
Experimental Models: Cell Lines
Mouse L-WRN cell line	ATCC	CRL-3276
Experimental Models: Organisms/Strains
Mouse/B6.129: KrasLSL-G12D	Jackson et al., 2001; The Jackson Laboratory	008179
Mouse/B6.129: Trp53flox/flox	Marino et al., 2000; The Jackson Laboratory	008462
Mouse/B6.129: Rosa26LSL-tdTomato	Madisen et al., 2010; The Jackson Laboratory	007905
Mouse/B6.129: Rosa26LSL-Luciferase	Safran et al., 2003; The Jackson Laboratory	005125
NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (aka NSG mice)	Ishikawa et al., 2005, The Jackson Laboratory	005557
Oligonucleotides
GusB qPCR F - CCGACCTCTCGAACAACCG	Roche Universal Probe Library	N/A
GusB qPCR R - GCTTCCCGTTCATACCACACC	Roche Universal Probe Library	N/A
Tigit qPCR F - TGCCTTCCTCGCTACAGG	Roche Universal Probe Library	N/A
Tigit qPCR R - TGCAGAGATGTTCCTCTTTGTATC	Roche Universal Probe Library	N/A
Slc4a11 qPCR F - CGAGGATCCAGAACAGACCT	Roche Universal Probe Library	N/A
Slc4a11 qPCR R - GAGATGTTTGTGCAAAGAAGGA	Roche Universal Probe Library	N/A
Epcam qPCR F - TGTCATTTGCTCCAAACTGG	Roche Universal Probe Library	N/A
Epcam qPCR R - GTTCTGGATCGCCCCTTC	Roche Universal Probe Library	N/A
Recombinant DNA
N/A
Software and Algorithms
Code generated as part of this study	This paper	https://github.com/matanhofree/lungTumorEvolution
Matlab (The Mathworks)	https://www.mathworks.com/	R2019a
R	https://cran.r-project.org/	v3.6.1
RSEM	https://github.com/deweylab/RSEM	v1.3.0
Cellranger (10X Genomics)	https://support.10xgenomics.com/	v3.1.0
Cellranger ATAC (10X Genomics)	https://support.10xgenomics.com/	v1.2.0
CNVkit	https://github.com/etal/cnvkit/	v0.9.6
fastp	https://github.com/OpenGene/	v0.20.0
ATAC-seq-pipeline	https://github.com/ENCODE-DCC/atac-seq-pipeline/	v1.5.4
Other
N/A