REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Mouse anti-E-Cadherin	BD Biosciences	Cat# 610181, RRID:AB_397580
Rabbit anti-Collagen I	Bioss	Cat# bs-10423R
Biotinylated hyaluronan binding protein	Hokudo	Cat# BC41
Rabbit anti-Collagen IV	Proteintech	Cat# 19674-1-AP, RRID:AB_2878595
Rabbit anti-Laminin-1+2	Abcam	Cat# ab7463, RRID:AB_305933
Rabbit anti-KRT80	Proteintech	Cat# 16835-1-AP, RRID:AB_1851273
Rabbit anti-AHNAK2	Atlas Antibodies	Cat# HPA004145, RRID:AB_1859546
Rabbit anti-AKAP12	Proteintech	Cat# 25199-1-AP, RRID:AB_2879954
Rabbit anti-Ki67	Abcam	Cat# ab15580, RRID:AB_443209
Rabbit anti-Cleaved Caspase-3 (Asp175)	Cell Signaling Technology	Cat# 9661, RRID:AB_2341188
Alexa Fluor 555 Goat anti Mouse IgG (H + L)	Thermo Fisher Scientific	Cat# A-21422, RRID:AB_2535844
Alexa Fluor 555 Goat anti Mouse IgG2a (H + L)	Thermo Fisher Scientific	Cat# A-21137, RRID:AB_2535776
Alexa Fluor 488 Donkey anti Rabbit IgG (H + L)	Thermo Fisher Scientific	Cat# R37118, RRID:AB_2556546
Alexa Fluor 555 Donkey Anti-Rat IgG (H + L)	Abcam	Cat# ab150154, RRID:AB_2813834
DyLight 488 Streptavidin	Vector Laboratories	Cat# SA-5488, RRID:AB_2336405
Biological samples
Surgical specimens of human colorectal cancer	Tokyo Medical and Dental University Hospital	Yoshihito Kano
Chemicals, peptides, and recombinant proteins
Growth factor reduced Matrigel	Corning	Cat# 356231
Cellmatrix Type I-A	Nitta Gelatin	Cat# 631-00651
Cellmatrix Type IV	Nitta Gelatin	Cat# 638-05921
HyStem	Sigma	Cat# HYS020-1KT
murine EGF	Peprotech	Cat# 315-09
murine Noggin	R&D systems	Cat# 1967-NG
murine R-spondin 1	R&D systems	Cat# 3474-RS
Murine Wnt3a	Abcam	Cat# ab81484
N-2 supplement	Gibco	Cat# 17502-048
B-27 supplement	Gibco	Cat# 17504-044
Nicotinamide	Sigma-Aldrich	Cat# 72340
N-Acetyl-L cysteine	Sigma-Aldrich	Cat# A9165
Gastrin I	Sigma-Aldrich	Cat# G9145
A83-01	Tocris	Cat# 2939
Prostaglandin E2	Nacalai Tesque	Cat# 29334-21
Bovine Serum Albumin	Sigma	Cat# A9576
Y-27632	Tocris	Cat# 1254
TNF-α	Peprotech	Cat# 300-01A
5-Fluorouracil	Selleck Chemicals	Cat# S1209
Oxaliplatin	Selleck Chemicals	Cat# S1224
Irinotecan (CPT-11)	Selleck Chemicals	Cat# S1198
TNF inhibitor	Calbiochem	Cat# 654256
TEAD inhibitor	Selleck Chemicals	Cat# E1329
Critical commercial assays
DNeasy Blood & Tissue Kits	Qiagen	Cat# 69504
RNeasy Micro Kit	Qiagen	Cat# 74004
SuperScriptⅢ Reverse Transcriptase	Invitrogen	Cat# 18080044
SYBR green master mix	Qiagen	Cat# 20415
Cell Titer 96 Aqueous One Solution Cell Proliferation Assay Kit	Promega	Cat# G3581
VECTASHIELD Antifade Mounting Medium with DAPI	Vector laboratories	Cat# H-1200-10
Phalloidin FITC Reagent	Abcam	Cat# ab235137
Deposited data
Bulk RNA-seq of human CRC patient tissue and organoids and cancer sheets	This study	SRA: PRJNA1044535
Bulk ATAC-seq of human CRC organoids and cancer sheets	This study	SRA: PRJNA1044535 Mendeley Data: https://doi.org/10.17632/gbfgn8kfh8.1
Experimental models: Cell lines
Human CRC Matrigel cancer organoid (3D MG)	This study	N/A
Human CRC cancer sheet (2D HC)	This study	N/A
L-WRN cells for L-WRN conditioned medium	ATCC	CRL-3276
Oligonucleotides
Primer: AHNAK2 Fwd: CAGCAGGGGGTAGCTTTCAA	This study	N/A
Primer: AHNAK2 Rev: CTTGCTGTTGCACCAAGTCC	This study	N/A
Primer: KRT80 Fwd: TTCGACCTCGGGCATCTCTA	This study	N/A
Primer: KRT80 Rev: AACTCCATGTCTGTGCGCTT	This study	N/A
Primer: AKAP12 Fwd: AGAAGAGGTTGTGGCCGAAG	This study	N/A
Primer: AKAP12 Rev: CCACCTCCGTTTTCTGCTCT	This study	N/A
Primer: F3 Fwd: AGCTTTTGAGGGGCTGACTT	This study	N/A
Primer: F3 Rev: GGAAGGTGCCCAGAATACCA	This study	N/A
Primer: CYR61 Fwd: CGCCTTGTGAAAGAAACCCG	This study	N/A
Primer: CYR61 Rev: GGTTCGGGGGATTTCTTGGT	This study	N/A
Primer: CTGF Fwd: GGGAAATGCTGCGAGGAGT	This study	N/A
Primer: CTGF Rev: TCCAGTCGGTAAGCCGC	This study	N/A
Primer: TACSTD2 Fwd: CCCCTTTCGGTCCAACAACA	This study	N/A
Primer: TACSTD2 Rev: AACTCCTCTTCTCCTCGGGT	This study	N/A
Primer: OLFM4 Fwd: AGCTGGAGGTGGAGATAAGAAA	This study	N/A
Primer: OLFM4 Rev: CTGAACCACAGACGGTTTGC	This study	N/A
Primer: SMOC2 Fwd: GGCACATCCACAAGGTACGA	This study	N/A
Primer: SMOC2 Rev: GTCCAGAACGCTGGTCAGAA	This study	N/A
Primer: LGR5 Fwd: CCTTCCAACCTCAGCGTCTT	This study	N/A
Primer: LGR5 Rev: AGGGATTGAAGGCTTCGCAA	This study	N/A
Software and algorithms
RIAS visualization tool	Rhelixa	https://www.rhelixa.com/rias/
R package – ClusterProfiler	Wu T et al.56	https://bioconductor.org/packages/release/bioc/html/clusterProfiler.html
ShinyGO v.0.77	Ge SX et al.57	http://bioinformatics.sdstate.edu/go/
Gene set enrichment analysis tool software (version; 4.3.0)	BROAD INSTITUTE	https://www.gsea-msigdb.org/gsea/index.jsp
Cytoscape software Version 3.9.1	Doncheva NT et al.58	http://cytoscape.org RRID:SCR_003032
Fiji	Schneider CA et al.59	http://fiji.sc RRID:SCR_002285
Adobe Photoshop (version 24.0.1 x64)	Adobe	https://www.adobe.com/jp/products/photoshop.html RRID:SCR_014199
GraphPad Prism software (version; 9.3.1)	GraphPad Prism	https://www.graphpad.com/RRID:SCR_002798
NDP.view2	Hamamatsu	Cat# U12388-01
IGV (version; 2.4.19)	Robinson JT et al.60	https://software.broadinstitute.org/software/igv/
Other
Coster 24-well Clear TC-treated Multiple Well Plates	Corning	Cat# 3524
Nunc 48-well Cell-Culture Treated Multidishes	Thermo Scientific Nunc	Cat# 150687
Falcon 96-well Clear Flat Bottom TC-treated Culture Microplate	Corning	Cat# 353072
EZVIEW Glass Bottom Culture Plate LB 24well	Iwaki	Cat# 5826-024
Matsunami 8-well Chamber Plate	Matsunami	Cat# SCS-N28
Matsunami 2-well Chamber Plate	Matsunami	Cat# SCS-N22
Tissue-Tek O.C.T. Compound	Sakura Finetek USA	Cat# 4583
High Profile Microtome Blade	Feather	Cat# FHP-01