REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit anti-Nanog	Abcam	Cat#ab21624; RRID: AB_446437
Mouse anti-TRA-1-60	Stem Cell Tech	Cat#60064; RRID: AB_2686905
Mouse anti-SSEA-4	Santa Cruz	Cat#sc-21704; RRID: AB_628289
Goat anti-Oct-3/4	Santa Cruz	Cat#sc-8628; RRID: AB_653551
Mouse anti-PAX6	DSHB	Cat#PAX6; RRID: AB_528427
Rabbit anti-OLIG2	Millipore	Cat#AB9610; RRID: AB_570666
Rabbit anti-Nestin	Abcam	Cat#ab92391; RRID: AB_10561437
Mouse anti-HB9	DSHB	Cat#81.5C10-c; RRID: AB_2145209
Mouse anti-ISL1/2	DSHB	Cat#39.4D5-c; RRID: AB_2314683
Goat anti-ChAT	Millipore	Cat#MAP144P; RRID: AB_2313845
Rabbit anti-VAChT	Sigma-Aldrich	Cat#SAB4200559; RRID: AB_2910560
Chicken anti-NF-H	EnCor Biotech	Cat#CPCA-NF-H; RRID: AB_2149761
Chicken anti-NF-H	Abcam	Cat#ab4680; RRID: AB_304560
Mouse anti-βIII-tubulin	Millipore	Cat#MAB5564; RRID: AB_11212768
Rabbit anti-Cleaved Caspase 3	Cell Signaling	Cat#9661; RRID: AB_2341188
Rabbit anti-TDP-43 (C-terminal)	Proteintech	Cat#12892-1-AP; RRID: AB_2200505
Rabbit anti-TDP-43 (N-terminal)	Proteintech	Cat#10782-2-AP; RRID: AB_615042
Mouse anti-pTDP-43 (Ser409/410)	Proteintech	Cat#66318-1-lg; RRID: AB_2881699
Rabbit anti-Vinculin	Abcam	Cat#ab129002; RRID: AB_11144129
Rabbit anti-Histone H3	Cell Signaling	Cat#4499; Clone D1H2; RRID: AB_10544537
Mouse anti-Actin	Millipore	Cat#MAB1501; Clone C4; RRID: AB_2223041
Rabbit anti-Synapsin I	Calbiochem	Cat#574777; RRID: AB_2200124
Mouse anti-PSD95	Millipore	Cat#MABN68; RRID: AB_10807979
Mouse anti-Synaptophysin	Sigma-Aldrich	Cat#S5768; RRID: AB_477523
Donkey anti-Mouse IgG DyLight® 488	Abcam	Cat#ab96875; RRID: AB_10698084
Donkey anti-Mouse IgG DyLight® 550	Abcam	Cat#ab96876; RRID: AB_10679663
Donkey anti-Mouse IgG DyLight® 650	Abcam	Cat#ab96878; RRID: AB_10680869
Donkey anti-Rabbit IgG DyLight® 488	Abcam	Cat#ab96891; RRID: AB_10679664
Donkey anti-Rabbit IgG DyLight® 650	Abcam	Cat#ab96894; RRID: AB_10680167
Donkey anti-Goat IgG Alexa Fluor® 488	Jackson Immunoresearch	Cat#705-545-147; RRID: AB_2336933
Donkey anti-Goat IgG Alexa Fluor® 647	Invitrogen	Cat#A21447; RRID: AB_2535864
Donkey anti-Chicken Alexa Fluor® 647	Jackson Immunoresearch	Cat#703-605-155; RRID: AB_2340379
HRP-conjugated anti-Mouse	Jackson Immunoresearch	Cat#115-035-003; RRID: AB_10015289
HRP-conjugated anti-Rabbit	Jackson Immunoresearch	Cat#111-035-144; RRID: AB_2307391
HRP-conjugated anti-Chicken	Jackson Immunoresearch	Cat#703-035-155; RRID: AB_10015283
Chemicals, peptides, and recombinant proteins
Matrigel	Corning Millipore	Cat#354277
Poly-L-ornithine (PLO)	Sigma-Aldrich	Cat#P3655
Laminin	Sigma-Aldrich	Cat#L2020
Laminin	Life Technologies	Cat#23017-015
Gentle Cell Dissociation Reagent	StemCell Technologies	Cat#07174
Accutase™	StemCell Technologies	Cat#07922
mTeSR1™	StemCell Technologies	Cat#85850
DMEM/F12 medium	Gibco	Cat#10565–018
Neurobasal medium	Life Technologies	Cat#21103–049
N2	Life Technologies	Cat#17502–048
B27	Life Technologies	Cat#17504–044
GlutaMAX™	Gibco	Cat#35050-061
Antibiotic-antimycotic	Gibco	Cat#15240–062
Ascorbic acid	Sigma-Aldrich	Cat#A5960
SB431542	Selleckchem	Cat#S1067
DMH1	Selleckchem	Cat#S7146
CHIR99021	Selleckchem	Cat#S2924
Retinoic acid (RA)	Sigma-Aldrich	Cat#R2625
Purmorphamine (PMN)	Sigma-Aldrich	Cat#SML-0868
Valproic acid (VPA)	Sigma-Aldrich	Cat#P4543
Compound E (CpdE)	StemCell Technologies	Cat#73954
Insulin-like growth factor-1 (IGF-1)	Peprotech	Cat#100–11
Brain-derived neurotrophic factor (BDNF)	Peprotech	Cat#450–02
Ciliary neurotrophic factor (CNTF)	Peprotech	Cat#450–13
Y-27632	Selleckchem	Cat#S1049
Normal donkey serum (NDS)	Millipore	Cat#S30-100
Bovine serum albumin (BSA)	Multicell	Cat#800–095-CG
Hoechst 33342 DNA dye	Life Technologies	Cat#H3570
Cytosine arabinoside (AraC)	Sigma-Aldrich	Cat#C6645
Glutamate	Sigma-Aldrich	Cat#G1626
Cyclothiazide (CTZ)	Tocris	Cat#0713
Ethacrynic acid (EA)	Sigma-Aldrich	Cat#SML1083
RIPA buffer	Millipore	Cat#20-188
Protease inhibitors	Roche	Cat#11697498001
Phosphatase inhibitors	Roche	Cat#04906837001
Tetrodotoxin (TTX)	Sigma-Aldrich	Cat#T8024
Critical commercial assays
Genomic DNA Mini kit	Geneaid	Cat#GB100
hPSC Genetic Analysis kit	StemCell Technologies	Cat#07550
P3 Primary Cell 4D Nucleofector™ X Kit S	Lonza	Cat#V4XP-3032
miRNeasy micro kit	Qiagen	Cat#217004
RNase-free DNase set	Qiagen	Cat#79256
M-MLV Reverse Transcriptase kit	ThermoFischer	Cat#28025013
TaqMan® Fast Advanced Master Mix	Applied Biosystems	Cat#A44360
Cell-Titer Glo® Luminescent Cell Viability Assay	Promega	Cat#G7570
DC Protein Assay	Bio-Rad	Cat#5000111
Clarity Western ECL Substrate	Bio-Rad	Cat#170-5061
Clarity Max Western ECL Substrate	Bio-Rad	Cat#1705062
Experimental models: Cell lines
AIW002-02 iPSCs	Chen et al.28	See Table S1
TARDBP A382T/AIW002-02 iPSCs	This study	See Table S1
TARDBP G348C/AIW002-02 iPSCs	This study	See Table S1
Oligonucleotides
sgRNAs	IDT	See Table S2
ssODNs	Synthego	See Table S2
Primers and affinity probes for ddPCR	IDT	See Table S3
Primers for Sanger sequencing	Invitrogen	See Table S3
TaqMan© probes	ThermoFischer	See Table S4
Software and algorithms
CellProfiler 4.0.7	Carpenter et al.103	https://cellprofiler.org/
GraphPad Prism 9.3.0	N/A	https://www.graphpad.com/features
AxIS Navigator 1.5.1.12	Axion Biosystems	https://www.axionbiosystems.com/products/mea/mea-software
Image Lab 6.0.1	Bio-Rad	https://www.bio-rad.com/en-ca/product/image-lab-software?ID=KRE6P5E8Z
JuLITM Stage software	NanoEntek	http://julistage.com/support/Download/