KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
NKX2.1	Abcam	Cat# ab76013; RRID:AB_1310784
RUNX2	Cell Signaling Technology	Cat# 12556S; RRID:AB_2732805
LGALS1	Cell Signaling Technology	Cat# 13888S; RRID:AB_2798338
HMGA2	Cell Signaling Technology	Cat# 8179S; RRID:AB_11178942
ZEB1	Abcam	Cat# ab87280; RRID:AB_2040541
RUNX1	Cell Signaling Technology	Cat# 8529S; RRID:AB_10950225
SFTPC	Millipore Sigma	Cat# AB3786; RRID:AB_91588
SFTPB	ThermoFisher	Cat# PA5-42000; RRID:AB_2609628
BATF	Sigma Aldrich	Cat# SAB4500122; RRID:AB_10745033
CAV1	Sigma Aldrich	Cat# C3237; RRID:AB_476842
HOPX	Proteintech	Cat# 11419-1-AP; RRID:AB_10693525
HSP90	BD Biosciences	Cat# 610418; RRID:AB_397798
RUNX3	Abcam	Cat# ab135248; RRID:AB_2848183
RFP	Rockland	Cat# 600-401-379; RRID:AB_2209751
Zfp795	Novus Biologicals	Cat# NBP2-20947; RRID:AB_2848184
Fra1	ThermoFisher	Cat# PA5-40361; RRID:AB_2609389
Onecut2	Proteintech	Cat# 21916-1-AP; RRID:AB_2848180
PDPN	Abcam	Cat# ab109059; RRID:AB_2848181
RUNX2	Abcam	Cat# ab23981; RRID:AB_777785
CD45	Abcam	Cat# ab10558; RRID:AB_442810
CD11B-APC	eBioscience	Cat# 7-0112-82; RRID:AB_469344
TER119-APC	BD Biosciences	Cat# 557909; RRID:AB_398635
CD45-APC	BD Biosciences	Cat# 559864; RRID:AB_398672
CD31-APC	Biolegend	Cat# 102510; RRID:AB_312917
Bacterial and Virus Strains
Ad5-Sftpc-Cre	University of Iowa viral vector core facility	Cat# VVC-Berns-1168
Biological Samples
Lung adenocarcinoma, 75 cases, tumor and matched NAT*, unstained slide	biomax	Cat# HLugA150CS02
Lung cancer progression tissue array, including TNM, clinical stage and pathology grade, 100 cases/100 cores, replacing LC1005	biomax	Cat # LC1005a
Lung disease spectrum (pulmonary cancer progression) tissue array, 193 cases/208 cores	biomax	Cat# LC2083
Chemicals, Peptides, and Recombinant Proteins
NP-40 Surfact-Amps Detergent Solution	Thermo Scientific Nalgene	Cat# 28324
Thermo Scientific Pierce Sequencing Grade Dimethylformamide	Thermo Fisher Scientific	Cat# 20673
0.5M EDTA pH 8.0	Thermo Fisher Scientific	Cat# 15575-020
Triton X-100	Sigma Aldrich	Cat# T8787-50ML
HEPES (1M)	Life Technologies	Cat# 15630-080
Tween(R)20, SigmaUltra	Sigma-Aldrich	Cat# P7949-100ML
NuPAGE MOPS SDS Running Buffer	Invitrogen	Cat# NP0001
TBS Buffer 20X Liquid, 4L	Amresco	Cat# J640-4L
RIPA Buffer	Thermo Fisher Scientific	Cat# 89900
Halt Phosphatase Inhibitor	Thermo Scientific	Cat# PI-78420
Halt Protease Inhibitor Cocktail (100X)	Thermo Scientific	Cat# 78430
NuPAGE LDS Sample Buffer (4X)	Life Technologies	Cat# NP0007
NuPAGE Sample Reducing Agent (10X)	Invitrogen	Cat# NP0009
NuPAGE Transfer Buffer (20X)	Life Technologies	Cat# NP0006-1
Blotting-Grade Blocker	Bio-Rad	Cat# 170-6404
Ponceau S	Sigma Aldrich	Cat# P7170-1L
NuPAGE Novex 4-12% Bis-Tris Protein Gels, 1.5mm, 10 well	Life Technologies	Cat# NP0335BOX
Amersham ECL Prime Western Blotting Detection Reagent	GE Healthcare	Cat# RPN2232
Dual Endogenous Enzyme Blocking Kit	Agilent Technologies	Cat# S200389-2
2.5% Normal Horse Serum Blocking Solution	Vector Laboratories	Cat# S-2012
ImmPRESS HRP Anti-Rabbit IgG (Peroxidase) Polymer	Vector Laboratories	Cat# mp-7401
ACK lysing buffer	Thermo Fisher Scientific	Cat# a10492-01
DMEM with L-Glutamine	VWR	Cat# 10-013-CV (45000-304)
0.25% Trypsin-EDTA (1X) Phenol Red	Invitrogen	Cat# 25200-114
RPMI 1640	VWR	Cat# 15-040-CV
Tet System Approved FBS	Clontech	Cat# 631106
Penicillin-Streptomycin	VWR	Cat# 45000-652
S-MEM	Life Technologies	Cat# 11380-037
RNase inhibitor	Thermo Fisher Scientific	Cat# N8080119
DPBS, 1X without calcium and magnesium	VWR Scientific Inc	Cat# 21-031-CV
10X PBS	VWR	Cat# AAJ67653-AP
Bovine Albumin Fraction V (7.5% solution)	Thermo Fisher Scientific	Cat# 15260037
Glycine	VWR	Cat# 97061-128
Collagenase from Clostridium histolyticum	Sigma-Aldrich	Cat# C9407-500MG
MgCl2 (1M)	Thermo Fisher Scientific	Cat# AM9530G
NaCl, 5M	ThermoFisher Scientific	Cat# AM9759
Tris, Hydrochloride	Santa Cruz Biotechnology	Cat# sc-216106A
Sodium Dodecyl Sulfate	Bio-Rad	Cat# 161-0302
Sybr Fast 2X MM LC480	Kapa Biosystems	Cat# KK4611
Thermo Scientific Pierce Methanol free Formaldehyde Ampules	Thermo Fisher Scientific	Cat# 28908
Proteinase K, Recombinant, PCR grade solution	Sigma-Aldrich	Cat# 3115828001
HBSS, no Calcium, no Magnesium, no Phenol Red	Thermo Fisher Scientific	Cat# 14175-079
Invitrogen DNase I	Thermo Fisher Scientific	Cat# 18-047-019
Collagenase, Type 4	Worthington Biochemical	Cat# LS004189
FastDigest Esp3I	Thermo Fisher Scientific	Cat# FD0454
Puromycin	Invitrogen	Cat# a11138-02
Zinc formalin fixative, pH 6.25	Electron Microscopy Sciences	Cat# 21516.375
Exonuclease I	New England Biolabs (NEB)	Cat# M0293S
Collagenase from Clostridium histolyticum	Sigma-Aldrich	Cat# C9407-500MG
ProLong Glass Antifade Mountant	Thermo Fisher Scientific	Cat# P36980
Digitonin	Promega	Cat# G9441
Critical Commercial Assays
Opal 4-Color Manual IHC Kit 50 slides	Akoya Biosciences	Cat# NEL810001KT
DAB Peroxidase Substrate Kit	Vector Labs	Cat# SK-4100
NEBNext High-Fidelity 2X PCR Master Mix	New England Biolabs (NEB)	Cat# M0541L
Pierce BCA Protein Assay Kit	Thermo Fisher -- Pierce	Cat# 23227
KAPA Library Quant for Illumina Sequencing Platforms	Kapa Biosystems	Cat# KK4824
MinElute PCR Purification Kit	Qiagen	Cat# 28006
Lung Dissociation Kit, mouse	Miltenyi Biotec	Cat# NC0315167
RNeasy Plus Mini Kit	Qiagen	Cat# 74134
High-Capacity cDNA reverse transcription kit	Thermo Fisher Scientific	Cat# 4368814
Qubit dsDNA HS Assay Kit	Thermo Fisher Scientific	Cat# Q32854
QIAGEN Plasmid Plus Midi Kit (25)	Qiagen	Cat# 12943
QIAquick Gel Extraction Kit (250)	Qiagen	Cat# 28706
SMARTer ThruPLEX DNA-Seq Kit - 24 Rxns	Takara Bio	Cat# R400674
ECM Cell Adhesion Array Kit, colorimetric	Millipore Sigma	Cat# ECM540
CD45 microbeads mouse	Miltenyi Biotec	Cat# 130-052-301
Mouse L308 Array, Membrane	RayBiotech	Cat# AAM-BLM-1A-2
Nextera DNA Library Preparation Kit	Illumina	Cat# FC-121-1030
NextSeq 500/550 High Output Kit v2	Illumina	Cat# FC-404-2002
NextSeq	Illumina	Cat# FC-404-2005
SureCell ATAC-Seq Library Preparation Kit	Bio-Rad	Cat# 17004620
Agencourt AMPure XP	Beckman Coulter	Cat# A63880
SureCell ddSEQ Index Kit	Bio-Rad	Cat# 12009360
Agilent High Sensitivity DNA Kit	Agilent	Cat# 5067-4626
TC20 Cell Counting Kit, with Trypan Blue	Bio-Rad	Cat# 1450003
Deposited Data
ScATAC-seq data	This manuscript	GSE134812
Early time point single cell data	This manuscript	GSE145192
Bulk-ATACseq	This manuscript	GSE151403
Visualization of UMAP scATAC-seq	This manuscript	https://buenrostrolab.shinyapps.io/lungATAC/
UCSC genome browser tracks for normal cells	This manuscript	http://genome.ucsc.edu/s/lmlafave/normal_lung_scATAC
UCSC genome browser tracks for tumor modules	This manuscript	http://genome.ucsc.edu/s/lmlafave/KPT_modules
Experimental Models: Cell Lines
860T3 KP cell line	This manuscript	N/A
1183T3 KP cell line	This manuscript	N/A
853T2 KP cell line	This manuscript	N/A
860T1 KP cell line	This manuscript	N/A
1183T4 KP cell line	This manuscript	N/A
932T2 KP cell line	This manuscript	N/A
932T3 KP cell line	This manuscript	N/A
932LN KP cell line	This manuscript	N/A
779T1 KP cell line	This manuscript	N/A
779T2 KP cell line	This manuscript	N/A
779LN KP cell line	This manuscript	N/A
Experimental Models: Organisms/Strains
KP mouse	Jackson et al., 2001, 2005	stock 008179, stock 008462
Tomato mouse (Ai9)	Jackson Labs	stock 007905
B6129SF1/J	Jackson Labs	stock 101043
Oligonucleotides
Genotyping primers	Table S7	N/A
RUNX2 control g1f: CACCGGGCCACGAGTTCGAGATCGA	This manuscript	N/A
RUNX2 control g1r: AAACTCGATCTCGAACTCGTGGCCC	This manuscript	N/A
RUNX2 OE sg1a: CACCGGAGGAGGAAATCGA	This manuscript	N/A
RUNX2 OE sg1b: AAACTCGATTTCCTCCTCC	This manuscript	N/A
RUNX2 OE sg2a: CACCGGGCGGAGTCTGCTG	This manuscript	N/A
RUNX2 OE sg2b: AAACCAGCAGACTCCGCCC	This manuscript	N/A
RUNX1 KO sg1a: CACCGAGGAGTACCTTGAAAGCGAT	This manuscript	N/A
RUNX1 KO sg1b: AAACATCGCTTTCAAGGTACTCCTC	This manuscript	N/A
RUNX1 KO sg4a: CACCGTAGCGAGATTCAACGACCTC	This manuscript	N/A
RUNX1 KO sg4b: AAACGAGGTCGTTGAATCTCGCTAC	This manuscript	N/A
RUNX2 KO sg3a: CACCGTGCGGACCAGTTCGGCCGGG	This manuscript	N/A
RUNX2 KO sg3b: AAACCCCGGCCGAACTGGTCCGCAC	This manuscript	N/A
RUNX2 KO sg4a: CACCGGCCCTCGGAGAGGTACCAGA	This manuscript	N/A
RUNX2 KO sg4b: AAACTCTGGTACCTCTCCGAGGGCC	This manuscript	N/A
RUNX3 KO sg1a: CACCGGGACGTGCTGGCCGACCACG	This manuscript	N/A
RUNX3 KO sg1b:AAACCGTGGTCGGCCAGCACGTCCC	This manuscript	N/A
Recombinant DNA
lentiCRISPR-V2-puro	Joung et al., 2017	Addgene #98290
Lenti-Sam-puro	This manuscript	N/A
Lenti-Cas9-blast	Sanjana et al., 2014	Addgene #52962
Software and Algorithms
Aiforia (NSCLC_v25 algorithm)	This manuscript	https://www.aiforia.com/
R (v3.5.3)	R Core Team, 2019	https://www.R-project.org
chromVAR R package (v0.2.0)	Schep et al., 2017	https://github.com/GreenleafLab/chromVAR
uwot R package (v0.1.4)	McInnes et al., 2018	https://github.com/jlmelville/uwot
survival R package (2.41-3)	Therneau and Grambsch, 2000	https://cran.r-project.org/web/packages/survival/index.html
GSEA (v3.0)	Subramanian et al., 2005	https://www.gsea-msigdb.org/gsea/index.jsp
ImageJ (v1.52k)	Schneider, et al., 2012	https://imagej.net/
ImageJ Protein Array Analyzer (v1.1.c)	Carpentier, 2010	https://imagej.net/macros/toolsets/Protein%20Array%20Analyzer.txt
FlowJo (v10.6.2)	N/A	www.flowjo.com
CaseViewer (v2.2.1)	N/A	https://www.3dhistech.com
MATLAB (v2019a)	Higham and Higham, 2016	https://www.mathworks.com
Ilastik (v1.3.3)	Berg et al., 2019	https://www.ilastik.org
MSigDB (v7.0)	Liberzon et al., 2015	https://www.gsea-msigdb.org/gsea/msigdb/index.jsp
bowtie2 (v2.3.3.1)	Langmead et al., 2012	http://bowtie-bio.sourceforge.net/bowtie2/index.shtml
MACS2 (v2.1.2)	Zhang et al., 2008	https://github.com/taoliu/MACS/
samtools (v1.9)	Li et al., 2009	http://samtools.sourceforge.net
Picard toolkit (2.14.1-SNAPSHOT)	N/A	http://broadinstitute.github.io/picard
biomaRt (v2.34)	Durinck et al., 2005	https://bioconductor.org/packages/release/bioc/html/biomaRt.html
ggfortify R package (v0.4.10)	Tang et al., 2016	https://github.com/sinhrks/ggfortify
BAP (v0.5.9i)	Lareau et al., 2019	https://github.com/caleblareau/bap
BWA (v0.7.15)	Li, 2013	https://github.com/lh3/bwa
QuPath (0.1.2)	Bankhead et al., 2017	https://qupath.github.io
Code generated for this manuscript	This study	https://github.com/buenrostrolab/lungATAC_analysis_code