REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rat monoclonal anti-Ki67, eFluor 570 conjugated	ThermoFisher Scientific	Cat# 41-5698-82; RRID: AB_11220285
Rat monoclonal anti-Ki67, FITC conjugated	ThermoFisher Scientific	Cat# 11-5698-82; RRID: AB_11151330
Rabbit polyclonal anti-EpCAM	Abcam	Cat# ab71916; RRID: AB_1603782
Rat monoclonal anti-mouse EpCAM, BV421 conjugated	Biolegend	Cat# 118225; RRID: AB_2563983
Goat polyclonal anti-Tacstd2 (Trop2)	R&D systems	Cat# AF1122; RRID: AB_2205662
Rabbit monoclonal anti-Tacstd2 (Trop2)	Abcam	Cat# ab214488; RRID: AB_2811182
Mouse monoclonal anti-Villin	Thermo Fisher	Cat# MA5-12227; RRID: AB_10980388
Rabbit polyclonal anti-Slc26a3	Novus Biologicals	Cat# NBP1-84450; RRID: AB_11031898
Goat polyclonal anti-Muc2	Santa Cruz	Cat# sc-13312; RRID: AB_2146672
Rabbit polyclonal anti-Chga	Abcam	Cat# ab15160; RRID: AB_301704
Rabbit polyclonal anti-RFP	Rockland	Cat# 600-401-379; RRID: AB_2209751
Chicken polyclonal anti-GFP	Abcam	Cat# ab13970; RRID: AB_300798
Rat monoclonal anti-Ly6a (Sca-1), FITC conjugated	Biolegend	Cat# 122505; RRID:AB_756190
Rat monoclonal anti-Ly6g	Biolegend	Cat# 127601; RRID: AB_1089179
Rabbit polyclonal anti-Actin	MilliporeSigma	Cat# A2066; RRID: AB_476693
Rat monoclonal anti-CD44, Alexa Fluor 488 conjugated	Biolegend	Cat# 103015; RRID: AB_493678
Mouse monoclonal anti-β-Catenin	BD Biosciences	Cat# 610154; RRID: AB_397555
Mouse monoclonal anti-phospho-Histone H3 (Ser10)	Cell Signaling Technology	Cat# 9706; RRID: AB_331748
Rabbit monoclonal anti-Hif1α	Abcam	Cat# ab179483; RRID: AB_2732807
Rabbit monoclonal anti-phospho-Perk	Cell Signaling Technology	Cat# 3179; RRID: AB_2095853
Rabbit monoclonal anti-Perk	Cell Signaling Technology	Cat# 3192; RRID: AB_2095847
Rabbit polyclonal anti-phospho-eIF2α	Cell Signaling Technology	Cat# 9721; RRID: AB_330951
Rabbit polyclonal anti-eIF2α	Cell Signaling Technology	Cat# 9722; RRID: AB_2230924
Rabbit polyclonal anti-phospho-IRE1α	ThermoFisher Scientific	Cat# PA1-16927; RRID: AB_2262241
Rabbit monoclonal anti-IRE1α	Cell Signaling Technology	Cat# 3294; RRID: AB_823545
Rabbit polyclonal anti-Hspa5 (BiP)	Cell Signaling Technology	Cat# 3183; RRID: AB_10695864
Rabbit polyclonal anti-Ero1l	Cell Signaling Technology	Cat# 3264; RRID: AB_823684
Mouse monoclonal anti-β-Actin	Abcam	Cat# ab6276; RRID: AB_2223210
Biological Samples
Formalin-fixed paraffin blocks of colonic resection/biopsy samples derived from patients with ulcerative colitis	Washington University in St. Louis Department of Pathology & Immunology	N/A
Chemicals, Peptides, and Recombinant Proteins
Tamoxifen	MilliporeSigma	Cat# T5648
Diphtheria toxin	MilliporeSigma	Cat# D0564
Dextran Sodium Sulfate	TbD Consultancy	Cat# DB001-500 g
2,4,6-Trinitrobenzenesulfonic acid (TNBS)	MilliporeSigma	Cat# 2297-10ML
Paraformaldehyde (32%)	Electron Microscopy Sciences	Cat# 15714
Tissue-Tek Oct Compound	Fisher Scientific	Cat# 50-363-579
Agar	MilliporeSigma	Cat# A7921
Trilogy	MilliporeSigma	Cat# 920P
Rhodamine-labeled UEA I	Vector Laboratories	Cat# RL-1062; RRID: AB_2336769
Protease/phosphatase inhibitor cocktail (100x)	Cell Signaling Technology	Cat# 5872S
Blocking One buffer	Nacalai	Cat# 03953-95
Superblock (TBS) blocking buffer	ThermoFisher Scientific	Cat# 37537
DNase1	MilliporeSigma	Cat# 10104159001
Dispase 1	MilliporeSigma	Cat# 11097113001
Collagenase 1	ThermoFisher Scientific	Cat# 17100-017
Sytox-Red	Biolegend	Cat# 425301
Propidium Iodide	Biolegend	Cat# 421301
Brefeldin A (BFA)	MilliporeSigma	Cat# B7651-5MG
Tunicamycin (TM)	MilliporeSigma	Cat# T7765-5MG
VH298	Abcam	Cat# ab230370
Dimethyloxaloylglycine (DMOG)	MilliporeSigma	Cat# 89464-63-1
(Z)-4-Hydroxytamoxifen	MilliporeSigma	Cat# H7904
Y-27632	R&D Systems	Cat# 1254
Matrigel	Corning	Cat# 354234
Trypsin (10x)	MilliporeSigma	Cat# T4549
Critical Commercial Assays
RNeasy Micro Kit	QIAGEN	Cat# 74004
iScript Reverse Transcription Supermix for RT-PCR	Bio-Rad	Cat# 1708841
TB Green Advantage qPCR Premix	Takara	Cat# 639676
VECTASTAIN Elite ABC HRP Kit	Vector Laboratories	Cat# PK-6100
DAB Peroxidase (HRP) Substrate Kit	Vector Laboratories	Cat# SK-4100
RNAscope Wash Buffer Reagents	ACDBio	Cat# 310091
RNAscope Target Retrieval Reagents	ACDBio	Cat# 322000
RNAscope H2O2 & Protease Plus	ACDBio	Cat# 2003382
RNAscope 2.5 HD Detection Reagents - Red	ACDBio	Cat# 2002657
Pierce BCA Protein Assay Kit	ThermoFisher Scientific	Cat# 23225
SuperSignal West Pico PLUS Chemiluminescent Substrate	ThermoFisher Scientific	Cat# 34580
SuperSignal West Femto Maximum Sensitivity Substrate	ThermoFisher Scientific	Cat# 34094
Click-iT EdU Cell Proliferation Kit for Imaging, Alexa Fluor 488 dye	ThermoFisher Scientific	Cat# C10337
Deposited Data
Raw data files for RNA sequencing	This paper	GEO: GSE127172
Experimental Models: Cell Lines
Mouse: L-WRN	Miyoshi and Stappenbeck, 2013; ATCC	Cat# CRL-3276
Mouse: C57BL/6J colonic spheroid line	This paper	N/A
Mouse: Lgr5-EGFP-IRES-CreERT2/Rosa-LSL-tdTomato colonic spheroid line	This paper	N/A
Mouse: Hopx-CreERT2/Rosa-LSL-tdTomato colonic spheroid line	This paper	N/A
Mouse: Hopx-CreERT2/Rosa-LSL-DTR colonic spheroid line	This paper	N/A
Mouse: Hopx-GFP colonic spheroid line	This paper	N/A
Mouse: Axin2-CreERT2-tdTomato colonic spheroid line	This paper	N/A
Experimental Models: Organisms/Strains
Mouse: C57BL/6J	The Jackson Laboratory	Cat# 000664
Mouse: BALB/cJ	The Jackson Laboratory	Cat# 000651
Mouse: B6.129P2-Lgr5tm1(cre/ERT2)Cle/J (Lgr5-EGFP-IRES-CreERT2)	The Jackson Laboratory	Cat# 008875
Mouse: Hopxtm2.1(cre/ERT2)Joe/J (Hopx-CreERT2)	The Jackson Laboratory	Cat# 017606
Mouse: Hopxtm3.1Joe/J (Hopx-GFP)	The Jackson Laboratory	Cat# 029271
Mouse: B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J (Rosa-LSL-tdTomato)	The Jackson Laboratory	Cat# 007909
Mouse: C57BL/6-Gt(ROSA)26Sortm1(HBEGF)Awai/J (Rosa-LSL-DTR)	The Jackson Laboratory	Cat# 007900
Mouse: Axin2tm1.1(cre/ERT2/tdTomato)Smr (Axin2-CreERT2-tdTomato)	Gift of E.E. Morrisey, University of Pennsylvania, Philadelphia, PA; Frank et al., 2016	N/A
Oligonucleotides
qPCR primers, see also Table S7	This paper	N/A
RNAscope Probe-Mm-Lgr5	ACDBio	Cat# 312171
RNAscope Probe-Mm-Hopx	ACDBio	Cat# 405161
RNAscope Probe-Hs-LGR5	ACDBio	Cat# 311021
RNAscope Probe-Hs-HOPX	ACDBio	Cat# 423001
Software and Algorithms
GSEA	Broad Institute; Subramanian et al., 2005	http://software.broadinstitute.org/gsea/index.jsp
Enrichr	Ma’ayan Laboratory, Icahn School of Medicine at Mount Sinai, New York, NY; Chen et al., 2013, Kuleshov et al., 2016	https://amp.pharm.mssm.edu/Enrichr/
EdgeR	Bioconductor	https://bioconductor.org/packages/release/bioc/html/edgeR.html
Limma	Bioconductor	http://bioconductor.org/packages/release/bioc/html/limma.html
GAGE	Bioconductor	https://bioconductor.org/packages/release/bioc/html/gage.html
ImageJ	NIH	https://imagej.nih.gov/ij/
Graphpad Prism 8	Graphpad	https://www.graphpad.com/scientific-software/prism/