Reagent or resource	Source	Identifier
Antibodies
Anti-β-actin (Mouse monoclonal)	Sigma	A5441; RRID: AB_476744
Anti-BAX [2D2] Mouse monoclonal	Abcam	Ab77566; RRID: AB_1565901
Anti-BAX (Rabbit polyclonal)	Cell Signaling Technology	#2772S; RRID: AB_10695870
Anti BAK [AT8B4] (Mouse monoclonal)	Abcam	Ab104124; RRID: AB_10712355
Anti-BAK (Rabbit polyclonal)	Cell Signaling Technology	#3814S; RRID: AB_2290287
Anti -BCL-xL [EPR16642] (Rabbit monoclonal)	Abcam	Ab178844; RRID: NA
Anti-BCL-xL (Rabbit polyclonal)	Cell Signaling Technology	#2762S; RRID: AB_10694844
Anti-BCL2 [EPR17509] (Rabbit monoclonal)	Abcam	Ab182858; RRID: AB_2715467
Anti-BCL2 (Rabbit polyclonal)	Cell Signaling Technology	#2876; RRID: AB_2064177
Anti-BIM (Rabbit polyclonal)	Cell Signaling Technology	#2819S; RRID: AB_10692515
Anti-Caspase 3 (Rabbit monoclonal)	Abcam	Ab13847; RRID: AB_443014
Anti-Caspase 3 (Rabbit polyclonal)	Cell Signaling Technology	#9662S; RRID: AB_10694681
Anti-GATA4 [6H10] (Mouse monoclonal)	Thermo Fisher Scientific	MA5-15532; RRID: AB_10989032
Anti-HNF1β (Goat polyclonal)	Abcam	Ab59118; RRID: AB_945772
Anti- HNF4α (Rabbit monoclonal)	Cell Signaling Technology	#3113S; RRID: AB_2295208
Anti-MCL1 (Rabbit polyclonal)	Cell Signaling Technology	#4572; RRID: AB_2281980
Anti-PAX6 [AD1.5] (Mouse monoclonal)	Millipore	Ab570718; RRID: AB_570718
Anti-PDX1 (Goat polyclonal)	R&D Systems	Af2419 RRID: AB_355257
Anti-PUMA (Rabbit polyclonal)	Cell Signaling Technology	#4976; RRID: AB_2064551
Anti-SFRP5 (Rabbit polyclonal)	Abcam	Ab230425; RRID: NA
Donkey Anti-Mouse IgG (H + L) Highly Cross-Adsorbed secondary antibody, Alexa Fluor Plus 647	Invitrogen	Ab32787 RRID: AB_2762830
Goat Anti-Mouse IgG HRP	Santa Cruz	sc-2005; RRID: AB_631736
Donkey Anti-Rabbit IgG (H + L) Alexa Fluor 488	Invitrogen	A21206; RRID: AB_2535792
Goat Anti-Rabbit IgG HRP	Santa Cruz	sc-2004; RRID: AB_631746
Donkey Anti-Goat IgG (H + L) Cross-Adsorbed, Alex Fluor 488	Thermo Fisher Scientific	A11055; RRID: AB_2534102
Donkey Anti-Mouse (H + L) Highly Cross-Adsorbed, Alex Fluor 488	Thermo Fisher Scientific	A21202; RRID: AB_141607
Bacterial and Virus Strains
N/A	N/A	N/A
Deposited Data
RNA-Seq	GEO	GSE136064
Experimental Models: Cell Lines
Mouse: CF-1 mouse embryonic fibroblasts	MTI-GlobalStem	GSC-6001G
HEK293FT	Thermo Fisher Scientific	R70007
Human ESC W09 (Female)	WiCell Research Institute, Inc	15-W0038
Human iPSCs iAGb (Male)	Reprogrammed from fibroblast AG16102, Coriell Institute	N/A
Oligonucleotides
QPCR primers, shRNA oligos, see Table S2	This paper	N/A
Chemical, peptides and recombinant proteins
Activin A	R&D system	338-AC-50
ALK5ill	ENZO	ALX-270-445-M001
Ascorbic acid	Sigma	A8960
Betacellulin	Cell Signaling	5235SF
B-27™ Serum Minus Vitamin A	Thermo Fisher Scientific	#12587010
β-mercaptoethanol	Thermo Fisher Scientific	21985-023
Calcium chloride	Sigma	C-5670
CHIR9021	Tocris	4423
CMRL 1066 Supplemented	Mediatech Inc	99-603-CV
CMRL Medium 1066	Life Technologies	11530-037
Collagenase IV	Life Technologies	17104019
DAKO mounting medium	DAKO	S3023
DAPI	Sigma	D9542
DAPT	Abcam	Ab120633
Dispase in DMEM/F12	STEMCELL Technologies	07923
D(+)-Glucose	WAKO	049-31165
Donkey serum	Merck	S-30
DMEM F12 media	Invitrogen	10565042
DMEM/High Glucose Media	Hyclone	SH30243.01
DMSO	Sigma	D2650
FAF-BSA	Proliant	68700
FGF2	Miltenyi Biotec	130-093-838
FGF7	Mitenyi Biotec	130037178
Gelatin (Porcine)	Sigma	G1890
GlutamaxTM Supplement	Invitrogen	35050038
HEPES Buffer 1 M	STEMCELL Technologies	07200
HyClone Phosphate Buffered Saline solution	GE Healthcare Life Sciences	SH30256.01
HycloneTM Fetal bovine serum (South America)	Hyclone	SV30160.03
ITS-X	Life Technologies	51500056
KnockOut™ serum replacement	Gibco	10828028
LDN193189	Sigma	SML0559
L-Glutamine	Sigma	G8540
LipofectamineTM 2000 Transfection Reagent	Invitrogen	11668027
LY294002	LC labs	L-7962
MCDB131	Life Technologies	10372019
MEM Non-Essential Amino Acids (100×)	Life Technologies	11140-050
M-PERTM Mammalian Protein Extraction Reagent	Thermo Scientific	78501
mTESRTM1 Basal Medium	STEMCELL Technologies	85851
NaHCO3	Sigma	S5761-500G
QVD-OPh	Cayman Chemical	15260
PDBu	Tocris	4153
Penicillin-Streptomycin	Thermo Fisher Scientific	15140122
Polybrene	Millipore	TR-1003-G
Retinoic Acid	WAKO	186-01114
RPMI-1640	Gibco	11875093
SANT1	Santa Cruz	Sc-203253
TeSRTM-E8TM Basal Medium	STEMCELL Technologies	05990
TeSRTM-E8TM 25X Supplement	STEMCELL Technologies	05992
TrypLE Express	Life Technologies	12604021
Trypsin-EDTA (0.25%)	Life Technologies	25200056
T3	Millipore	642511
Vitamin B3 (Nicotinamide)	Sigma	N0636-100G
Vitamin C (L-Ascorbic acid)	WAKO	012-04802
WEHI-539	ApexBio	A3935
XXI (Gamma-Secretase Inhibitor)	Millipore	565790
Y-27632	STEMCELL Technologies	72302
Critical commercial assays
High Capacity cDNA Reverse Transcription Kit	Applied Biosystems	4368813
iTaq™ Universal SYBR® Green Supermix	Bio-Rad	1725124
Lenti-XTM p24 Rapid Titer Kit	Clontech	632200
LIVE/DEAD® Viability/Cytotoxicity Kit	Thermo Fisher Scientific	L-3224
NucleoBond® Xtra Midi	Macherey-Nagel	740410.50
Nucleospin® Plasmid EasyPure	Macherey-Nagel	740727.250
Phusion High-Fidelity DNA Polymerase	Thermo Fisher Scientific	F530S
PierceTM BCA Protein Assay Kit	Thermo Fisher Scientific	23227
PureLinkTM Quick PCR Purification Kit	Invitrogen	K310002
RNA isolation Nucleospin® RNA	Macherey-Nagel	740955.250
Seahorse XF Base Medium	Agilent	102353-100-100
Seahorse XF Glycolysis Stress Test Kit	Agilent	103020-100
Seahorse XF Mito Stress Kit	Agilent	103015-100
SuperSignalTM West Dura Extended Duration Substrate	Thermo Fisher Scientific	34076
Softwares and Algorithms
AxioVision LE	Zeiss	Version 4.8.2
FlowJo 10	FlowJo	Version 10
Seahorse XFe96 Analyzer	Agilent	S7800B
Seahorse Wave Desktop Software	Agilent	Version 2.6.1
Others
CFX384TM Real-Time System	Bio-Rad	1855485
Coverslips 18 × 18 mm	Marienfeld	0101030
NanoDrop 1000 spectrophotometer	Thermo Fisher Scientific	V 3.8
Nikon Eclipse Inverted	Nikon	TS-100
Olympus Fluoview 1000 Inverted Confocal	Olympus	FV1000
Optima L-100 XP Ultracentrifuge	Beckman Coulter	L-100 XP
SuperFrost Plus™ Adhesion slides	Thermo Fisher Scientific	10149870
SW28 Ti Swinging-Bucket Aluminum Rotor	Beckman Coulter	342207
Ultra-Clear tubes	Beckman Coulter	344058