REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
HUWE1	Bethyl Laboratories	A300-486A; RRID:AB_2264590
p53	ThermoFisher Scientific	MA5-12571; RRID:AB_10986581
p21	ThermoFisher Scientific	33-7000; RRID:AB_2533135
Tubulin	Sigma-Aldrich	T9026; RRID:AB_477593
β-Actin	Sigma-Aldrich	A1978; RRID:AB_476692
Dye-conjugated secondary antibodies	Li-COR Bioscienecs	N/A
OCT4	Cell signaling	C30A3; RRID:AB_2167691
SSEA4	Cell signaling	MC813; RRID:AB_1264259
NESTIN	Abcam	ab22035; RRID:AB_446723
TUJ1	Covance	MMS-435P; RRID:AB_2313773
Ki67	Abcam	ab15580; RRID:AB_443209
Donkey anti-Mouse, Alexa Fluor 488	Invitrogen	A21202; RRID:AB_141607
Goat anti-Rabbit, Alexa Fluor 594	Invitrogen	A11037; RRID:AB_2534095
Bacterial and virus strains
E.coli BL21-CodonPlus (DE) RP	Agilent	230255
Chemicals, peptides, and recombinant proteins
Halt Protease and Phosphatase Inhibitors Cocktail	Thermo Scientific	78445
Accutase	STEMCELL Technologies	07922
mTesR.1 medium	STEMCELL Technologies	85850
E8 medium	Thermo Scientific	A1517001
DMEM/F12 medium	GIBCO	11330057
NEUROBASAL-A medium	GIBCO	10888022
Knock-out serum replacement (KSOR)	GIBCO	10828-028
Glutamax	Invitrogen	35050-038
MEM non-essential amino acids	Sigma	M7145
Y27632 (Rock inhibitor)	Merck	688000-100MG
Noggin	R & D Systems	1967-NG-025
2-mercaptoethanol	GIBCO	31350-010
B27 supplement, 50x	GIBCO	17504-044
B27 supplement (50x), minus vitamin A	GIBCO	12587-010
N2 supplement (100x)	GIBCO	175020-01
Ascorbic acid	Merck	A8960-5G
BDNF	R&D Systems	248-BDB-050
P53	Milipore	23-034
GDNF	R&D Systems	212-GD-050
dibutyryl-cAMP	Sigma	D0627-250MG
Critical commercial assays
SENSE mRNA-Seq library prep kit	Lexogen GmbH, Vienna, Austria	001.96
Mag-Bind RXNPure Plus beads	Omega Bio-tec, GA, USA	M1386-01
KAPA Library Quantification Kit	Roche	7960204001
Agilent High Sensitivity DNA Kit on a Bioanalyzer	Agilent Technologies, CA, USA	5067-4626
cBot Cluster Generation System on HiSeq4000 flowcells	Illumina Inc., CA, USA	SY-301-2002
Dead Cell Apoptosis Kit	Molecular Probes	V13241
hPSC Genetic Analysis Kit	Stem Cell Technologies	07550
Deposited data
RNA sequencing of healthy control and patient LCs	GEO	GEO: GSE130551
Experimental models: Cell lines
Healthy individual LCLs (GM03798, GM07535, GM16113, GM16119)	Coriell Cell Repository (Coriell Institute for Medical Research, USA)	N/A
XLID LCLs with HUWE1 duplication, or HUWE1 p.R2981H and p.R4187C mutations	Bosshard et al.13	N/A
JMS1 and JMS2 and WT LCLs with mutation HUWE1 p.G4310R	Friez et al.4	N/A
JMS1 patient-derived human induced pluripotent stem cells (hiPSCs)	Applied StemCell (California, USA)	N/A
Healthy control hiPSCs	ATCC, Manassas, USA CRL(S)23—in Siller et al.42	ATCC-DYS0100
Oligonucleotides
Listed in Table S1.		N/A
Recombinant DNA
shControl; pLKO.1 puro	Addgene	8453
shp53 pLKO.1 puro shRNA	Addgene	19119
shp53 pLKO.1 puro shRNA-427	Addgene	25636
shp53 pLKO.1 puro shRNA-941	Addgene	25637
pET28-HECT	Parsons et al.43	N/A
Software and algorithms
bcl2fastq 2.20.0.422	Illumina, Inc., CA, USA	N/A
STAR aligner	Dobin et al.44	v2.4.0
htseq-count	Anders et al.45	v0.6.0
limma voom	Ritchie et al.46	N/A
DAVID (Database for Annotation, Visualization, and Integrated Discovery, v6.8)	Huang et al.47	N/A
FlowJo™	LLC software	v. 10.6.1
Fiji ImageJ	National Institute of Health	v. 1.53c
iMaris	Bitplane	v. 8.2.1
Other
RNeasy mini kit	QIAGEN	74106
MultiScribe Reverse Transcriptase	ThermoFisher Scientific	4311235
Power SYBR Green PCR Master Mix	Applied Biosystems	43-676-59
Illumina HiSeq4000 instrument	Illumina, Inc., CA, USA	N/A
BD FACSAria II	BD Biosciences	N/A
U-bottom ultra-low attachment 96-well plates	Corning	CLS7007
Costar 24-well plates, flat bottom, ultra-low attachment	Corning	CLS3473-24EA
Matrigel	BD Biosciences	356234
Zeiss LSM 510 Meta live Confocal system	Zeiss	N/A
EVOS FL Auto Cell Imaging System	ThermoFisher Scientific	AMF5000