REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Mouse monoclonal anti-human CD45	BioLegend	Cat# 304023; RRID: AB_493760
Mouse monoclonal anti-human CD31	BioLegend	Cat#303121; RRID: AB_2562148
Donkey polyclonal anti-rabbit IgG	BioLegend	Cat#406410; RRID: AB_10897810
Mouse monoclonal anti-human CD24	BioLegend	Cat#311135; RRID: AB_2566578
Goat polyclonal anti-mouse IgG	BioLegend	Cat#405308; RRID: AB_315011
Rat monoclonal anti-human PDPN	BioLegend	Cat#337011; RRID: AB_2561308
Mouse monoclonal anti-human EpCAM	BioLegend	Cat#324205; RRID: AB_756079
Mouse monoclonal anti-human CD74	eBioscience	Cat#11-0748-41; RRID: AB_2043845
Recombinant human IgG1 anti-human fibroblast antigen	Miltenyi	Cat#130-100-139; RRID: AB_2651744
Rabbit polyclonal anti-human FDCSP	abcam	Cat#ab121420; RRID: AB_11127721
Mouse monoclonal anti-human SOX6	abcam	Cat#ab84880; RRID: AB_1861338
Mouse monoclonal anti-human ZEB1	Atlas Antibodies	Cat#AMAb90510; RRID: AB_2665569
Rabbit polyclonal anti-human ZEB2	Atlas Antibodies	Cat#HPA003456; RRID: AB_10603840
Goat polyclonal anti-human LIGHT/TNFSF14	R and D Systems	Cat#AF664; RRID: AB_355512
Goat polyclonal anti-human/mouse COX-2	Bio-Techne	Cat#AF4198; RRID: AB_2229909
Goat polyclonal anti-human Coagulation Factor III/Tissue Factor	Bio-Techne	Cat#AF2339; RRID: AB_442150
Mouse monoclonal anti-human SOX6	Bio-Techne	Cat#MAB7759, RRID: AB_2737259
Goat polyclonal anti-human/mouse Bcl-6	Bio-Techne	Cat#AF5046; RRID: AB_2063454
Mouse monoclonal anti-human CD55/DAF	Bio-Techne	Cat#MAB20091; RRID: AB_2075960
Goat polyclonal anti-human CCL21/6Ckine	Bio-Techne	Cat#AF366; RRID: AB_355327
Mouse monoclonal anti-human CCL19/MIP-3 beta	Bio-Techne	Cat#MAB361; RRID: AB_2071417
Sheep polyclonal anti-human Podoplanin	Bio-Techne	Cat#AF3670; RRID: AB_2162070
Mouse monoclonal anti-human ZEB1	Bio-Techne	Cat#MAB6708; RRID: AB_10972647
Mouse monoclonal anti-human ZEB2/SIP1	Bio-Techne	Cat#MAB73782; RRID: AB_2737260
Mouse monoclonal anti-human IL-33 (6H617)	Bio-Techne	Cat#NBP2-27333; RRID: AB_2737261
Mouse monoclonal anti-human/mouse/rat alpha -Smooth Muscle Actin	Bio-Techne	Cat#MAB1420; RRID: AB_262054
Goat polyclonal anti-human PDGF R alpha	Bio-Techne	Cat#AF-307-NA; RRID: AB_354459
Mouse monoclonal anti-human Clusterin	Bio-Techne	Cat#MAB2937; RRID: AB_2229755
Rat anti-human/Mouse Periostin/OSF-2 Antibody	Bio-Techne	Cat#MAB3548; RRID: AB_2252599
Mouse monoclonal anti-F3	Atlas Antibodies	Cat#AMAb91235; RRID:AB_2665858
Rabbit polyclonal anti-SMAD7	Atlas Antibodies	Cat#HPA028897; RRID: AB_10600811
Rat monoclonal anti-CD45R (RA3-6B2)	Abcam	Cat#ab64100; RRID: AB_1140036
Mouse monoclonal anti-CD45 (2B11 + PD7/26)	Agilent (Dako)	Cat#M0701; RRID: AB_2314143
Mouse monoclonal anti-human CD90	BioLegend	Cat#328107; RRID: AB_893438
Anti-Human CD326/EpCAM (9C4)-141Pr	Fluidigm	Cat#3141006B; RRID: AB_2687653
Anti-Human CD45 (HI30)-Y89	Fluidigm	Cat#3089003B; RRID: AB_2661851
Anti-Human CD31/PECAM-1 (WM59)-145Nd	Fluidigm	Cat#3145004B; RRID: AB_2737262
Maxpar X8 Antibody Labeling Kit, 144Nd	Fluidigm	Cat#201144B
Maxpar X8 Antibody Labeling Kit, 146Nd	Fluidigm	Cat#201146B
Maxpar X8 Antibody Labeling Kit, 150Nd	Fluidigm	Cat#201150B
Maxpar X8 Antibody Labeling Kit, 151Eu	Fluidigm	Cat#201151B
Maxpar X8 Antibody Labeling Kit, 152Sm	Fluidigm	Cat#201152A
Maxpar X8 Antibody Labeling Kit, 154Sm	Fluidigm	Cat#201154B
Maxpar X8 Antibody Labeling Kit, 159Tb	Fluidigm	Cat#201159B
Maxpar X8 Antibody Labeling Kit, 160Gd	Fluidigm	Cat#201160B
Maxpar X8 Antibody Labeling Kit, 162Dy	Fluidigm	Cat#201162B
Maxpar X8 Antibody Labeling Kit, 164Dy	Fluidigm	Cat#201164B
Maxpar X8 Antibody Labeling Kit, 166Er	Fluidigm	Cat#201166B
Maxpar X8 Antibody Labeling Kit, 167Er	Fluidigm	Cat#201167B
Maxpar X8 Antibody Labeling Kit, 168Er	Fluidigm	Cat#201168B
Maxpar X8 Antibody Labeling Kit, 169Tm	Fluidigm	Cat#201169B
Maxpar X8 Antibody Labeling Kit, 172Yb	Fluidigm	Cat#201172B
Maxpar X8 Antibody Labeling Kit, 173Yb	Fluidigm	Cat#201173B
Maxpar X8 Antibody Labeling Kit, 175Lu	Fluidigm	Cat#201175B
Maxpar X8 Antibody Labeling Kit, 176Yb	Fluidigm	Cat#201176B
Biological Samples
Human intestinal tissue biopsies	University of Oxford Translational Gastroenterology Unit	https://www.expmedndm.ox.ac.uk/tgu/tgu-biobank-ibd-cohort
Murine colon	Epistem	This study
Chemicals, Peptides, and Recombinant Proteins
4′,6-Diamidine-2′-phenylindole dihydrochloride	Sigma Aldrich	Cat#10236276001
Dispase II, powder	ThermoFisher Scientific	Cat#17105041
Matrigel Basement Membrane Matrix Growth Factor Reduced (GFR) Phenol Red-Free LDEV-Free	Corning	Cat#356231
SB 431542	R&D Systems	Cat#1614/10
Y-27632 dihydrochloride	R&D Systems	Cat#1254/10
CTS GlutaMAX-I Supplement	ThermoFisher Scientific	Cat#A1286001
N-2 Supplement (100X)	ThermoFisher Scientific	Cat#17502048
B-27 Supplement (50X), serum free	ThermoFisher Scientific	Cat#17504044
NICOTINAMIDE	Sigma Aldrich	Cat#N0636
Recombinant Human EGF	PeproTech	Cat#AF-100
Recombinant Human IL-6	R&D Systems	Cat#206-IL-010
Recombinant Human LIGHT/TNFSF14	R&D Systems	Cat#664-LI-025
A 83-01	R&D Systems	Cat#2939/10
[LEU15]-Gastrin I HUMAN	Sigma Aldrich	Cat#G9145
Prostaglandin E2	Sigma Aldrich	Cat#P0409
N-Acetylcysteine	Sigma Aldrich	Cat#A9165
Recombinant Human R-Spondin-1	PeproTech	Cat#120-38
Recombinant Murine Noggin	PeproTech	Cat#250-38
2.5% Normal Goat Serum	Vector Laboratories	Cat#S-1012
ImmPRESS HRP Anti-Rabbit IgG (Peroxidase) Polymer Detection Kit, made in Goat	Vector Laboratories	Cat#MP-7451; RRID: AB_2631198
ImmPRESS HRP Anti-Mouse IgG (Peroxidase) Polymer Detection Kit, made in Goat	Vector Laboratories	Cat#MP-7452
ImmPRESS-AP Anti-Rabbit IgG (alkaline phosphatase) Polymer Detection Kit	Vector Laboratories	Cat#MP-5401; RRID: AB_2336536
ImmPRESS-AP Anti-Mouse IgG (alkaline phosphatase) Polymer Detection Kit	Vector Laboratories	Cat#MP-5402; RRID: AB_2336535
ImmPACT DAB Peroxidase (HRP) Substrate	Vector Laboratories	Cat#SK-4105; RRID: AB_2336520
Vector Blue Alkaline Phosphatase (Blue AP) Substrate Kit	Vector Laboratories	Cat#SK-5300; RRID: AB_2336837
ImmPACT VIP Peroxidase (HRP) Substrate	Vector Laboratories	Cat#SK-4605; RRID: AB_2336525
Dako Liquid Permanent Red	Agilent (Dako)	Cat#K0640
Lab Vision Ultra V Block	Fisher scientific	Cat#12583158
ACK Lysing Buffer	Thermo Fisher	Cat#A1049201
Bovine Serum Albumin	Sigma	Cat#A1933
CellTracker Green CMFDA Dye	Thermo Fisher	Cat#C7025
CellTracker Orange CMRA Dye	Thermo Fisher	Cat#C34551
Collagenase VIII	Sigma Aldrich	Cat#C2139
DMEM	Sigma	Cat#D5671
Dextran Sodium Sulfate (DSS)	MP Biomedicals	Cat#M9147
UltraPure 0.5M EDTA, pH 8.0	Thermo Fisher	Cat#15575020
Foetal Bovine Serum	Sigma	Cat#F9665
HBSS, no calcium, no magnesium	Thermo Fisher	Cat#14170112
HEPES solution	Sigma	Cat#H0887
LIVE/DEAD Fixable Dead Cell Stain	Thermo Fisher	Cat#L10120
NucBlue Live Reagent	Thermo Fisher	Cat#R37605
Percoll	GE Healthcare	Cat#17-0891-01
Propidium Iodide Solution	BioLegend	Cat#421301
Critical Commercial Assays
Foxp3 / Transcription Factor Staining Buffer Set	eBioscience	Cat#00-5523-00
Cytofix/Cytoperm	BD Biosciences	Cat#554714
Lightning-Link APC Antibody Labeling Kit	Novus Biologicals	Cat#705-0030
Lightning-Link R-PE Antibody Labeling Kit	Novus Biologicals	Cat#703-0030
Click-iT EdU Alexa Fluor 647 Imaging Kit	ThermoFisher Scientific	Cat#C10340
RNeasy Mini Kit (250)	QIAGEN	Cat#74106
iScript cDNA Synthesis Kit	Bio-Rad	Cat#1708891
RNAscope 2.5 HD Reagent Kit - BROWN	ACD Europe SRL	Cat#322300
Maxpar Nuclear Antigen Staining Buffer Set	Fluidigm	Cat#201063
Maxpar Cell Staining Buffer	Fluidigm	Cat#201068
CD45 Microbeads, human	Miltenyi Biotec	Cat#130-045-801
CD45 MicroBeads, mouse	Miltenyi Biotec	Cat#130-052-301
CD235a MicroBeads, human	Miltenyi Biotec	Cat#130-050-501
CD326 (EpCAM) MicroBeads, human	Miltenyi Biotec	Cat#130-061-101
CD326 (EpCAM) MicroBeads, mouse	Miltenyi Biotec	Cat#130-105-958
Chromium Single Cell 3′ Library & Gel Bead Kit v2	10X Genomics	Cat#120237
LD Columns	Miltenyi Biotec	Cat#130-042-901
Nextera XT DNA Library Preparation Kit	Illumina	Cat#FC-131-1096
SMARTer Ultra Low RNA Kit	Clontech	Cat#634832
Umbilical Cord Dissociation Kit human	Miltenyi Biotec	Cat#130-105-737
Chromium Single Cell 3′ Library & Gel Bead Kit v2	10X Genomics	Cat#PN-120237
Cell-ID Cisplatin-194Pt	Fluidigm	Cat#201194
EQ Four Element Calibration Beads	Fluidigm	Cat#201078
Cell-ID Intercalator-Ir	Fluidigm	Cat#201192A
Deposited Data
Single-cell RNaseq data	This study	GEO: GSE95459
Single-cell RNaseq data	This study	GEO: GSE114374
Experimental Models: Cell Lines
L Wnt-3A (male)	ATCC	Cat#CRL-2647; RRID:CVCL_0635
RAW 264.7 (male)	ATCC	Cat#TIB71; RRID:CVCL_0493
Experimental Models: Organisms/Strains
C57BL/6 male mice	Envigo Laboratories	RRID:IMSR_JAX:000664
Oligonucleotides
LGR5	ThermoFisher Scientific	Cat#Hs00969422_m1
OLFM4	ThermoFisher Scientific	Cat#Hs00610344_m1
AXIN2	ThermoFisher Scientific	Cat#Hs00610344_m1
NOTCH1	ThermoFisher Scientific	Cat#Hs01062014_m1
ALDH1A1	ThermoFisher Scientific	Cat#Hs00946916_m1
SOX9	ThermoFisher Scientific	Cat#Hs00165814_m1
MSI1	ThermoFisher Scientific	Cat#Hs01045894_m1
KRT20	ThermoFisher Scientific	Cat#Hs00300643_m1
MUC2	ThermoFisher Scientific	Cat#Hs03005103_g1
CDX2	ThermoFisher Scientific	Cat#Hs01078080_m1
HPRT1	ThermoFisher Scientific	Cat#Hs02800695_m1
GAPDH	ThermoFisher Scientific	Cat#Hs02786624_g1
RNAscope Probe - Hs-ADAMDEC1	ACD Europe SRL	Cat#478471
RNAscope Probe - Hs-DCN	ACD Europe SRL	Cat#589521
RNAscope Probe - Hs-SLIT2	ACD Europe SRL	Cat#466221
RNAscope Probe - Hs-CXCL12	ACD Europe SRL	Cat#422991
RNAscope Probe - Hs-F3	ACD Europe SRL	Cat#407611
RNAscope Probe - Hs-HSD17B2	ACD Europe SRL	Cat#467271
RNAscope Probe - Hs-POSTN	ACD Europe SRL	Cat#409181
RNAscope Probe - Hs-FRZB	ACD Europe SRL	Cat#412391
RNAscope Probe - Hs-WNT5A	ACD Europe SRL	Cat#604921
RNAscope Probe - Hs-WNT5B	ACD Europe SRL	Cat#423041
RNAscope Probe - Hs-BMP2	ACD Europe SRL	Cat#430641
RNAscope Probe - Hs-BMP5	ACD Europe SRL	Cat#472461
RNAscope Probe - Hs-FDCSP	ACD Europe SRL	Cat#444231
Software and Algorithms
ComBat sva Version 3.28.0	R Bioconductor	RRID: SCR_012836; https://bioconductor.org/packages/release/bioc/html/sva.html
CellRanger Version 2.0 Version 2.1.1	10X Genomics	https://support.10xgenomics.com/single-cell-gene-expression/software/downloads/latest
Seurat Version 1.4.0.16 Version 2.3.0	R Bioconductor	RRID: SCR_016341; https://www.satijalab.org/seurat
Scran Version 1.2.0 Version 1.6.9	R Bioconductor	https://github.com/MarioniLab/scran
Caret Version 6.0-80	CRAN	https://cran.r-project.org/web/packages/caret/index.html
DMrW Version 0.4.1	CRAN	https://cran.r-project.org/web/packages/DMwR/index.html
Biomart Version 92	Ensembl	RRID: SCR_002344; https://www.ensembl.org/biomart/martview/
pROC Version 1.12.1	CRAN	https://cran.r-project.org/web/packages/pROC/index.html
clusterProfiler Version 3.8.1	R Bioconductor	https://github.com/GuangchuangYu/clusterProfiler
Destiny Version 2.10.2	R Bioconductor	https://www.helmholtz-muenchen.de/icb/destiny
FastQC (v0.10.1)	Babraham Bioinformatics	RRID: SCR_014583; http://www.bioinformatics.babraham.ac.uk/projects/fastqc/
FeatureCounts (v1.5.0)	Source Forge	RRID: SCR_012919; http://subread.sourceforge.net
HISAT (v2.0.3b)	Kim et al., 2015	RRID: SCR_015530; https://ccb.jhu.edu/software/hisat/index.shtml
MultiQC (v0.7)	Ewels et al., 2016	RRID: SCR_014982; http://multiqc.info
NMF (v0.20.6)	CRAN	https://cran.r-project.org/web/packages/NMF/index.html
Picard Tools (v2.3.0)	Github	RRID: SCR_006525; http://broadinstitute.github.io/picard/
RUVSeq (v1.8.0)	Github	RRID: SCR_006263; https://github.com/drisso/RUVSeq
scater (v1.2.0)	Github	RRID: SCR_015954; https://github.com/davismcc/scater
Skewer	Github	RRID: SCR_001151; https://github.com/relipmoc/skewer
RTsne	CRAN	RRID: SCR_016342; https://cran.r-project.org/web/packages/Rtsne/index.html
WGCNA (v1.51)	CRAN	RRID: SCR_003302; https://cran.r-project.org/web/packages/WGCNA/index.html
RandomForest Version 4.6	CRAN	RRID: SCR_015718; https://cran.r-project.org/web/packages/randomForest/index.html
Other
ACD HybEZ Hybridization System (220v)	ACD Europe SRL	Cat#310013
Hg38 reference genome	UCSC	http://hgdownload.cse.ucsc.edu/goldenPath/hg38/bigZips/
Mm10 reference genome	UCSC	http://hgdownload.cse.ucsc.edu/goldenPath/mm10/bigZips/