REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit polyclonal H3K27ac - ChIP	Abcam	Cat# ab4729; RRID:AB_2118291
Rabbit polyclonal MED1 - ChIP	Bethyl Laboratories	Cat# A300-793A; RRID:AB_577241
Goat Anti-Mouse polyclonal Carboxypeptidase a1 - IF	R and D Systems	Cat# AF2765, RRID:AB_2085841
Rabbit anti-mouse monoclonal Cleaved Caspase-3 (Asp175) (5A1E) - IF	Cell Signaling Technology	Cat# 9664, RRID:AB_2070042
Rabbit anti-mouse monoclonal CDX2 (D11D10) - IF	Cell Signaling Technology	Cat# 12306, RRID:AB_2797879
Mouse monoclonal Anti-Cadherin, E - IF	BD Biosciences	Cat# 610181, RRID:AB_397580
Guinea Pig polyclonal Anti-Glucagon - IF	Millipore	Cat# 4031-01F, RRID:AB_433707
Polyclonal Rabbit Anti-Human Glucagon - IF	Dako (now Agilent)	Cat# A0565, RRID:AB_10013726
Rabbit monoclonal HES1 (D6P2U) - IF	Cell Signaling Technology	Cat# 11988, RRID:AB_2728766
Rabbit polyclonal HNF-1beta (H-85), discontinued- IF	Santa Cruz Biotechnology	Cat# sc-22840, RRID:AB_2279595
Goat anti-human polyclonal HNF1B/TCF2 - IF	Novus	Cat# NB100-57093, RRID:AB_843965
Guinea pig polyclonal Insulin - IF	Dako (now Agilent)	Cat# A0564, RRID:AB_10013624
Goat anti-mouse polyclonal Kirrel2/NEPH3 - IF	R and D Systems	Cat# AF2930, RRID:AB_2265276
Mouse monoclonal MNR2/HB9/Mnx1 - IF	DSHB	Cat# 81.5C10, RRID:AB_2145209
Rabbit polyclonal Mucin 1 (H-295), discontinued - IF	Santa Cruz Biotechnology	Cat# sc-15333, RRID:AB_2148554
Sheep Anti-Human polyclonal Neurogenin-3 - IF	R and D Systems	Cat# AF3444, RRID:AB_2149527
Mouse monoclonal Nkx2.2 - IF	DSHB	Cat# 74.5A5, RRID:AB_531794
Mouse monoclonal Nkx6.1 - IF	DSHB	Cat# F55A10, RRID:AB_532378
Mouse monoclonal Pax6 - IF	DSHB	Cat# pax6, RRID:AB_528427
Rabbit monoclonal non-phospho (Active) β-Catenin (Ser45) (D2U8Y) – IF	Cell Signaling Technology	Cat# 19807, RRID:AB_2650576
Mouse Anti-Rat monoclonal Pdx1 IF	DSHB	Cat# F6A11, RRID:AB_1157904
Rabbit polyclonal Phospho-Histone H3 (Ser10) - IF	Cell Signaling Technology	Cat# 9701, RRID:AB_331535
Rabbit polyclonal Phospho-Myosin Light Chain 2 (Ser19) - IF	Cell Signaling Technology	Cat# 3671, RRID:AB_330248
Goat polyclonal Somatostatin (D-20), discontinued - IF	Santa Cruz Biotechnology	Cat# sc-7819, RRID:AB_2302603
Polyclonal Sox9 – IF	Millipore	Cat# AB5535, RRID:AB_2239761
Rabbit Glu2 -IF	Gift from Bernard Thorens' lab (UNIL)	NA
Guinea pig Hb9/Mnx1 -IF	Gift - Samuel Pfaff’s lab (Salk Institute)	NA
Guinea pig Neurogenin3 – IF	Gift - Michael S German's lab (UCSF)	NA
Mouse Pdx1 – IF	Gift – Chris Wright’s lab (Vanderbilt University)	NA
Goat Ptf1a – IF	Gift – Chris Wright’s lab (Vanderbilt University)	NA
Rabbit Ptf1a – IF	Gift - Bertrand Blondeau’s lab (UPMC)	NA
Mouse Anti-CD184 (CXCR4) Monoclonal Antibody, Phycoerythrin Conjugated, Clone 12G5 - Flow cytometry	BD Biosciences	Cat# 555974; RRID:AB_396267
Mouse IgG2a, kappa Isotype Control, Phycoerythrin Conjugated, Clone G155-178 antibody - Flow cytometry	BD Biosciences	Cat# 563023; RRID:AB_2716792
Mouse Anti-PDX1 Phycoerythrin Conjugated - Flow cytometry	BD Biosciences	Cat# 562161; RRID:AB_10893589
Mouse Anti-NKX6-1 Alexa Fluor 647 Conjugated - Flow cytometry	BD Biosciences	Cat# 563338; RRID:AB_2738144
Mouse Anti-NKX6.1 Phycoerythrin Conjugated - Flow cytometry	BD Biosciences	Cat# 555574; RRID:AB_395953
Mouse-Anti-C-peptide-647 - Flow cytometry	BD Biosciences	Cat# 565831; RRID:AB_2739371
Mouse IgG1, kappa Isotype Control, Phycoerythrin Conjugated, Clone MOPC-21 - Flow cytometry	BD Biosciences	Cat# 555749; RRID:AB_396091
Mouse IgG1 kappa isotype control Alexa 647 Conjugated - Flow cytometry	BD Biosciences	BD Biosciences Cat# 557714; RRID:AB_396823
Chemicals, peptides, and recombinant proteins
Ascorbid acid	Sigma	Cat# A4544
Nicotinamide	Sigma	Cat# N0636
Heparin	Sigma	Cat# H3149-25KU
Zinc Sulfate	Sigma	Cat# Z0251-100G
NaHCO3	Sigma	Cat# S5761
Glucose	SIGMA	Cat# G8769-100ML
BSA	Lampire	Cat# 7500804
Insulin-Transferrin-Selenium-Ethanolamine (ITS -X) (100X)	Life Technologies	Cat# 51500-056
Sodium pyruvate solution 100mM	Merck lifescience SLU	Cat# S8636-100ML
Chemically Defined Lipid Concentrate	Life Technologies	Cat# 11905031
Trace Elements A	Corning	Cat# 25-021-CI
Trace Elements B	Corning	Cat# 25-022-CI
GlutaMax	Life Technologies	Cat# 35050038
MCDB 131 Medium, no glutamine	Life Technologies	Cat# 10372-019
Corning™ CMRL 1066	Fisher Scientific	Cat# Corning™ 15-110-CV
Y-27632 2HCl (ROCKi)	Selleckchem	Cat# S1049
Matrigel Growth Factor Reduced	Corning	Cat# 356231
0.5 mM EDTA	ThermoFisher	Cat# 15575
FGF7	Genscript	Cat# Z03407-1
CHIR	Tocris	Cat# 4423
ActivinA	Qkine	Cat# QK001 ActA_1000
Human EGF	Peprotech	Cat# AF-100-15
Retinoic acid	Sigma	Cat# R2625
TPB (amyloid precursor protein modulator)	Santa Cruz Biotechnology	Cat# sc-204424
SANT-1	Sigma	Cat# S4572
LDN-193189	Selleckchem	Cat# S2618
RepSox	Selleckchem	Cat# S7223
Human Betacellulin	Peprotech	Cat# 100-50-100UG
T3	Sigma	Cat# T6397-100MG
N-Acetyl Cysteine (NAC)	Sigma	Cat# A9165-5G
ZM447439	Selleckchem	Cat# S1103
Gamma Secretase Inhibitor XX (GSiXX)	Calbiochem	Cat# 565789
Exendin-4	Enzo	Cat# ENZ-PRT111-0001
Essential 8	Life Technologies	Cat# A1517001
Critical commercial assays
Glucomen Areo glucose sensing strips	Menarini Diagnostics	Cat#47950
Ultra Mouse Insulin ELISA Kit	Crystal Chem	Cat#90080
Insulin High Range Assay kit	Perkin Elmer - cisbio	Cat#62IN1PEG
DirectPCR Lysis Reagent	Viagen Biotech	Cat#102-T
DreamTaq Green PCR Master Mix	Thermo Fisher Scientific	Cat#K1081
Phusion Green High-Fidelity DNA Polymerase	Thermo Fisher Scientific	Cat#F534S
Normal Donkey Serum	Jackson ImmunoResearch	Cat#017-000-121
TSA amplification kit	Invitrogen/Molecular Probes	Cat#T30955
Fluorescence Mounting Medium	Dako (now Agilent)	Cat#S3023
UltraPure™ Low Melting Point Agarose	Thermo Fisher Scientific	Cat# 16520050
benzyl alcohol	Sigma	Cat#108006-100ML
benzyl benzoate	Sigma	Cat#B6630-250ML
Antibody Diluent with Background Reducing Components	Dako (now Agilent)	Cat#S3022
NucleoSpin RNA Plus Kit	Macherey Nagel	Cat# 22740984.50
Transcriptor First Strand cDNA Synthesis Kit	Life Science Roche	Cat#04897030001
LightCycler 480 SYBR Green IMasterMix	Life Science Roche	Cat# 04707516001
SMART-Seq v4 Ultra low input RNA kit	Takara Bio	Cat#634890
Chromium Single Cell 3′ Library & Gel Bead Kit v3	10x Genomics	Cat#PN-1000075
Chromium Single Cell ATAC Library & Gel Bead Kit	10x Genomics	Cat#PN-1000110
Deposited data
Human MPCs ChIP-seq raw and processed reads	This paper	GEO: GSE183674
Human MPCs ChIP-seq processed reads	This paper	Mendeley Repository, https://doi.org/10.17632/xnckzpgxj8.1
Mouse MPCs scRNA-Seq and scATAC-Seq	This paper	GEO: GSE183674
Experimental models: Cell lines
Human: H1 (WA01)human embryonic stem cell line (hPSCReg ID: WAe001-A; NIH approval number NIHhESC-10-0043)	WiCell	Cat# WA01
Experimental models: Organisms/strains
Mouse: C57BL/6J	The Jackson Laboratory	RRID: IMSR_JAX:000664
Mouse: Tg(Sox9-EGFP)EB209Gsat/Mmucd	MMRRC (Gong et al., 2003)	RRID:MMRRC_011019-UCD
Mouse: Ptf1a n.567_837del line (abbreviated to Ptf1aenhΔ/enhΔ)	This paper	NA
Oligonucleotides
RNA sequence: mouse Ptf1a enhancer 5’gRNA1: ATCAGCCACACAATGTAATC	This paper	NA
RNA sequence: mouse Ptf1a enhancer 3’gRNA1: CCCTTCAATTGGCCGTTTTT	This paper	NA
RNA sequence: human PTF1A enhancer 5’gRNA1: GACTCTTTAAGTGGCTTGTC	This paper	NA
RNA sequence: human PTF1A enhancer 5’gRNA2: TGTCAATAGCACCTAATTAC	This paper	NA
RNA sequence: human PTF1A enhancer 3’gRNA3: GTAATTATCCAAGAGAGCAC	This paper	NA
RNA sequence: human PTF1A enhancer 3’gRNA4: TTAATCCCCTTAGAGTAACA	This paper	NA
qRT-PCR PTF1A F/R (TTATCCGAACAGCCAAAGTCTGGACC; AGTCTGGGACCTCTCAGGACACAA)	This paper	NA
qRT-PCR PDX1 F/R (AAGTCTACCAAAGCTCACGCG; CGTAGGCGCCGCCTGC)	This paper	NA
qRT-PCR NKX6-1 F/R (TATTCGTTGGGGATGACAGAG; TGGCCATCTCGGCAGCGTG)	This paper	NA
qRT-PCR SOX9 F/R (ATCAAGACGGAGCAGCTGAG; GGCTGTAGTGTGGGAGGTTG)	This paper	NA
qRT-PCR NKX2-2 F/R (GAACCCCTTCTACGACAGCA; ACCGTGCAGGGAGTACTGAA)	This paper	NA
qRT-PCR FOXA2 F/R (AAGACCTACAGGCGCAGCT; CATCTTGTTGGGGCTCTGC)	This paper	NA
qRT-PCR GATA4 F/R (GAGGAAGGAGCCAGCCTAGCAG; CGGGTCCCCCACTCGTCA)	This paper	NA
qRT-PCR ONECUT1 F/R (CGCTCCGCTTAGCAGCATG; GCTGGACATCTGTGAAGACC)	This paper	NA
qRT-PCR KI67 F/R (CGACCCTACAGAGTGCTCAA; TGCTCCTTCACTGGGGTCTT)	This paper	NA
qRT-PCR INS F/R (CAGAAGCG TGGCATTGTGGA; GCTGCGTCTAGTTGCAGTAG)	This paper	NA
qRT-PCR GCG F/R (GAAGGCGAGATTTCCCAGAAG; CCTGGCGGCAAGATTATCAAG)	This paper	NA
qRT-PCR NEUROG3 F/R (GACGACGCGAAGCTCACCAA; TACAAGCTGTGGTCCGCTAT)	This paper	NA
Software and algorithms
HOMER	Heinz et al., 2010	http://homer.salk.edu/homer/
Cutadapt v1.9.1	Martin, 2011	https://pypi.python.org/pypi/cutadapt/1.9.1
Trimgalore v0.4.1	NA	https://www.bioinformatics.babraham.ac.uk/projects/trim_galore/
Bowtie2 v2.1.0	Langmead and Salzberg, 2012	http://bowtie-bio.sourceforge.net/bowtie2/index.shtml
Samtools v1.2	Li et al., 2009	http://samtools.sourceforge.net
BEDTools	Quinlan and Hall, 2010	https://github.com/arq5x/bedtools2
MACS2	Zhang et al., 2008	https://github.com/taoliu/MACS
bedgraphToBigWig	NA	https://github.com/ENCODE-DCC/kentUtils
DESeq2 v1.10.1	Love et al., 2014	https://www.bioconductor.org/packages/DESeq2
Cellranger v3.0.2	10x Genomics	https://support.10xgenomics.com/single-cell-gene-expression/software/overview/welcome
Cellranger-atac v1.2.0	10x Genomics	https://support.10xgenomics.com/single-cell-atac/software/overview/welcome
Seurat v3.1.4	Stuart et al., 2019	https://github.com/satijalab/seurat
Signac v1.1.0	Stuart et al., 2021	https://github.com/timoast/signac/
Sinto v0.4.2	NA	https://timoast.github.io/sinto/
ImageJ	Schneider et al., 2012	https://imagej.nih.gov/ij/
Other
Infinite M200 plate reader	Tecan	NA
MZ16F stereomicroscope	Leica	NA
SP5 confocal microscope	Leica	NA
Single Plane Illumination Microscopy	Luxendo MuVi SPIM CS	NA
NEPA21 Super Electroporator	Nepagene	NA
LightCycler® 480 Instrument II	Roche	NA
Bioanalyzer	Agilent	NA
Islet perifusion chamber	BIOREP Technologies	Cat# PERI-CHAMBER
Perifusion chamber filter	BIOREP Technologies	Cat# PERI-FILTER
Perifusion chamber rubber ring	BIOREP Technologies	Cat# PERI-O-RING
Perifusion steel nozzle	BIOREP Technologies	Cat# PERI-NOZZLE
8-channel peristaltic pump	ISMATEC	Cat# ISM931A
Two-stop color code tube 0.38mm ID Tygon R3607	ISMATEC	Cat# 070534-03i / SC0003
Connecting tube 1.016mm ID Tygon 3603	ISMATEC	Cat# SC0035