REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Recombinant Anti-Collagen I Antibody	Abcam	Cat# ab270993; RRID:AB_2927551
Anti-β-catenin Antibody (E−5)	Santa Cruz	sc-7963; RRID:AB_626807
E-cadherin Antibody (H-108)	Santa Cruz	sc-7870; RRID:AB_2076666
Recombinant Anti-Ki67 antibody [SP6]	Abcam	ab16667; RRID:AB_302459
P-Histone H2A.X (Ser 139)	Santa Cruz	sc-517348; RRID:AB_2783871
Lysozyme Polyclonal Antibody	Invitrogen	PA5-16668; RRID:AB_10984852
MUC2 Monoclonal Antibody (996/1)	Invitrogen	MA5-12345; RRID:AB_10975230
Occludin Monoclonal Antibody (OC-3F10)	Invitrogen	33–1500; RRID:AB_2533101
Vimentin Monoclonal Antibody (3H9D1)	Proteintech	60330-1-Ig; RRID:AB_2881439
ZO-1 antibody [N2C1], Internal	GeneTex	GTX108627 RRID:AB_10731582
Goat Anti-Rabbit Alexa Fluor 488 Antibody	Abcam	Cat# 150077 RRID: AB_2630356
Goat Anti-Mouse Alexa Fluor 488 Antibody	Invitrogen	A11001; RRID:AB_2534069
Goat Anti-Rabbit Alexa Fluor 594 Antibody	Invitrogen	A11012; RRID:AB_2534079
Goat Anti-Rabbit Alexa Fluor 488 Antibody	Abcam	Cat# 150077 RRID: AB_2630356
Bacterial strains
Adherent-Invasive E. coli LF82	Arlette Darfeuille-Michaud	N/A
Chemicals, peptides, and recombinant proteins
MEM	Corning	Cat# MT 10-010-CV
Collagenase Type I	Thermo Fisher	Cat# 17100017
Collagenase Type II	Thermo Fisher	Cat# 17101015
Collagenase Type IV	Thermo Fisher	Cat# 17104019
HBSS with Ca2+/Mg2+	Thermo Fisher	Cat# 14-025-092
HBSS without Ca2+/Mg2+	Thermo Fisher	Cat# 14-175-095
MEM Non-Essential Amino Acids	Thermo Fisher	Cat# 11-140-050
Intestigro™ [L-WRN conditioned media, for intestine and colon PDOs]	UC San Diego HUMANOID™ Center	Cat# HUM2019
Tailor-2-Gro™ [L-WRN conditioned media, base]		Cat# HUM202420
Sodium Pyruvate	Sigma-Aldrich	Cat# S8636
Ciprofloxacin Hydrochloride	Corning	Cat# 61-277-RF
Antibiotic Antimycotic	Sigma-Aldrich	Cat# A5955
Trypsin (2.5%)	Thermo Fisher	Cat# 15090046
Zinc Formalin	Fisher Scientific	Cat# 23-313096
Xylene	VWR	Cat# XX0060-4
Hematoxylin	Sigma-Aldrich Inc	Cat# MHS1
Ethanol	Koptec	Cat# UN1170
Sodium Citrate	Sigma-Aldrich	Cat# W302600
DAB (10x)	Thermo Fisher	Cat# 1855920
Stable Peroxidase substrate buffer (10x)	Thermo Fisher	Cat# 34062
3% Hydrogen Peroxide	Target	Cat# 245-07-3628
Horse Serum	Vector Labs	Cat# 30022
Paraformaldehyde 16% Solution, EM Grade	Electron Microscopy Sciences	Cat# 15710
100% Methanol	Supelco	Cat# MX0485
Glycine	Fisher Scientific	Cat# BP381-5
Bovine Serum Albumin	Sigma-Aldrich	Cat# A9647-100G
Triton X-100	Sigma-Aldrich	Cat# X100-500ML
Prolong Glass	Invitrogen	Cat# P36984
Nail Polish (Rapid Dry)	Electron Microscopy Sciences	Cat# 72180
Gill Modified Hematoxylin (Solution II)	Millipore Sigma	Cat# 65066-85
Histogel	Thermo Scientific	Cat# HG4000012
TrypLE Select	Thermo Scientific	Cat# 12563-011
Advanced DMEM/F-12	Thermo Scientific	Cat# 12634-010
HEPES Buffer	Life Technologies	Cat# 15630080
Glutamax	Thermo Scientific	Cat# 35050-061
Penicillin-Streptomycin	Thermo Scientific	Cat# 15140-122
Matrigel	Corning	Cat# 354234
DPBS	Thermo Scientific	Cat# 14190-144
Ultrapure Water	Invitrogen	Cat# 10977-015
EDTA	Thermo Scientific	Cat# AM9260G
Fetal Bovine Serum	Sigma-Aldrich	Cat# F2442-500ML
Cell Recovery Solution	Corning	Cat# 354253
Sodium Azide	Fisher Scientific	Cat# S227I-100
Cyto-Fast Fix/Perm Buffer Set	BioLegend	Cat# 426803
FITC-Dextran	Sigma-Aldrich	Cat# FD10S
Ethyl alcohol, pure	Sigma-Aldrich	Cat# E7023
TRI Reagent	Zymo Research	Cat# R2050-1-200
Metformin	Sigma	Cat# D150959-5G
Pacritinib	Selleck Chem	Cat# S8057
Quercetin	Sigma Aldrich	Cat# Q4951
TP53 Inhibitor (p53i; Pifithrin-α-HBr)	Adipogen Life Science®	Cat# AG-CR1-0004-M005
Hylak Forte™	Amazon.com	N/A
Critical commercial assays
BrdU Cell Proliferation ELISA Kit (colorimetric)	Abcam	Cat# ab126556
DNA/RNA oxidative damage ELISA kit	Cayman Chemical, USA	Cat # 589320
SPiDER-βGal	Dojindo	Cat# SG02-10
TUNEL Assay Kit - BrdU-Red	Abcam	Cat# ab66110
Quick-RNA MicroPrep Kit	Zymo Research	Cat# R1051
Quick-RNA MiniPrep Kit	Zymo Research	Cat# R1054
HRP Horse Anti-Rabbit IgG Polymer Detection Kit	Vector Laboratories	Cat# MP-7401
Oligonucleotides
2x SYBR Green qPCR Master Mix	Bimake	Cat# B21203
qScript cDNA SuperMix	Quanta Biosciences	Cat# 95048
Deposited data
RNA sequencing data of PDOs from the colons of patients with CD and UC (or healthy controls)	This paper	GEO: GSE192819
RNA sequencing data of intestinal mucosal biopsies colon from IBD patients with infliximab treatment	Arijs et al.85	GEO: GSE16879
RNA sequencing data from CD patients	Corraliza et al.86	GEO: GSE115390
RNA sequencing data of inflamed intestinal mucosa of inflammatory bowel disease patients	Verstockt et al.87	E-MTAB-7604
Software and algorithms
ImageJ	ImageJ	RRID:SCR_003070
GraphPad Prism	GraphPad Prism	RRID:SCR_002798
MSD® DISCOVERY WORKBENCH 4.0	MSD	N/A
LAS AF Software	LAS AF Software	N/A
QuantStudio Design & Analysis Software	QuantStudio Design & Analysis Software	N/A
CIBERSORTx	CIBERSORTx	N/A
FlowJo	Flow Jo V10, BD BioSciences	RRID:SCR_008520
Other
6-well Tissue Culture Plate	Genesee Scientific	Cat# 25-105
12-well Tissue Culture Plate	CytoOne	Cat# CC7682-7512
Transwell Inserts (6.5 mm, 0.4 μm pore size)	Corning	Cat# 3470
Cell Scraper	Millipore Sigma	Cat# C5981-100EA
Millicell EZ Slide 8-Well Chamber	Millipore Sigma	Cat# PEZGS0816
Trypan Blue Stain	Invitrogen	Cat# T10282
70 μm Cell Strainer	Thermo Fisher Scientific	Cat# 22-363-548
Noyes Spring Scissors - Angled	Fine Science Tools	Cat# 15013-12
gentleMACS™ C Tubes	Miltenyi Biotec	Cat# 130-093-237
DAPI	Invitrogen	Cat# D1306 RRID: AB_2629482
Phalloidin, Alexa Fluor 594	Invitrogen	Cat# A12381 RRID: AB_2315633
Propidium Iodide	Invitrogen	Cat# V-13245 B
Countess II Automated Cell Counter	Thermo Fisher Scientific	AMQAX1000
Epithelial Volt-Ohm (TEER) Meter	Millipore	MERS00002
Automated TEER measurement system [REMS AutoSampler]	World Precision Instruments (WPI)	N/A
MESO QuickPlex SQ 120	MSD	N/A
Leica TCS SPE Confocal	Leica Microsystems	TCS SPE
Power Pressure Cooker XL	Tristar Products	N/A
Canon Rebel XS DLSR	Canon	N/A
MiniAmp Plus Thermal Cycler	Applied Biosystems	Cat# A37835
QuantStudio5	Applied Biosystems	Cat# A28140 RRID:SCR_020240
Light Microscope (brightfield images)	Carl Zeiss LLC	Axio Observer, Inverted; 491917-0001-000
Fisherbrand™ 150 Handheld Homogenizer	Fisher Scientific	Cat# 15340168
Spark 20M Multimode Microplate Reader	Tecan	N/A
NanoQuant Infinite M200	Tecan	N/A
Guava® easyCyte Benchtop Flow Cytometer	Millipore	Guava easyCyte 6 2L
MESO QuickPlex instrument	Mesoscale Discovery Inc.	SQ 120
gentleMACS™ Dissociator	Miltenyi Biotec	Cat# 130-093-235