REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit polyclonal anti-MAP-2	Millipore	Cat# AB5622-I; RRID: AB_2800501
Rabbit polyclonal anti-synapsin I	Sigma-Aldrich	Cat# S193; RRID: AB_261457
Rabbit polyclonal anti-Tyrosine Hydroxylase, N1C1	GeneTex	Cat# GTX102424; RRID: AB_2038197
Rabbit polyclonal anti-VGLUT1	Proteintech	Cat# 55491-1-AP; RRID: AB_2881348
Rabbit monoclonal anti-NeuN	Abcam	Cat# ab177487; RRID: AB_2532109
Mouse monoclonal anti-drebrin, M2F6	MBL	Cat# D029-3; RRID: AB_591275
Mouse monoclonal anti-PSD-95, 6G6-1C9	Thermo Fisher	Cat# MA1-045; RRID: AB_325399
Mouse monoclonal anti-NF-H	BioLegend	Cat# 801601; RRID: AB_2564641
Mouse monoclonal anti-beta III tubulin, 2G10	Abcam	Cat# ab78078; RRID: AB_2256751
Mouse monoclonal anti-GAD67, 1G10.2	Millipore	Cat# MAB5406; RRID: AB_2278725
Alexa Fluor 594 conjugated goat anti-rabbit	Thermo Fisher	Cat# A32740; RRID: AB_2762824
Alexa Fluor 488 conjugated goat anti-mouse	Thermo Fisher	Cat# A32723; RRID: AB_2633275
Biological samples
Quick-Neuron Excitatory - Human iPSC-derived Neurons (F, 74 yr donor) - Healthy Control	Elixirgen Scientific	Cat# EX-SeV-CW50065
Total RNA from the CIRM iPS cell line CW50065	Elixirgen Scientific	N/A (provided as a gift)
Chemicals, peptides, and recombinant proteins
Poly(ethyleneimine) solution	Sigma-Aldrich	Cat# 181978
Pierce 20X Borate Buffer	Thermo Fisher	Cat# 28341
Laminin Mouse Protein, Natural	Thermo Fisher	Cat# 23017015
DPBS, no calcium, no magnesium	Thermo Fisher	Cat# 14190144
Geltrex LDEV-Free Reduced Growth Factor Basement Membrane Matrix	Thermo Fisher	Cat# A1413202
Quick-Neuron Excitatory - Maintenance Medium	Elixirgen Scientific	Cat# 2EX-MM
Y-27632 2HCl	Selleckchem	Cat# S1049
Neurobasal Plus Medium	Thermo Fisher	Cat# A3582901
B-27 Plus Supplement (50x)	Thermo Fisher	Cat# A3582801
CultureOne Supplement (100X)	Thermo Fisher	Cat# A3320201
Neuron Culture Medium	Wako Chemicals	Cat# 148-09671
L(+)-Ascorbic Acid	Wako Chemicals	Cat# 012-04802
GlutaMAX Supplement	Thermo Fisher	Cat# 35050-061
Penicillin-Streptomycin	Thermo Fisher	Cat# 15140122
RNaseZap RNase decontamination solution	Ambion	Cat# AM9780
Nuclease-free water	Invitrogen	Cat# 10977023
β-Mercaptoethanol, 14.3 M	Sigma	Cat# M6250-100mL
Tris buffer, pH 8.0, 1 M	Ambion	Cat# 9010
Tween 20	Sigma	Cat# P9416-100ML
Magnesium chloride, 1 M	Ambion	Cat# 9010
RNase inhibitor, cloned 40 U μl-1	Ambion	Cat# AM2682
Triton X-100	Sigma-Aldrich	Cat# T8787-100ML
dNTP mix 10 mM each	Thermo Fisher	Cat# 18427-088
Superscript II reverse transcriptase	Thermo Fisher	Cat# 18064-014
Betaine for Molecular Biology	Wako Chemicals	Cat# 028-16294
KAPA HiFi HotStart ReadyMix 2×	KAPA Biosciences	Cat# KK26010
Ethanol, molecular biology grade	Wako Chemicals	Cat# 054-07225
Agencourt AMPure XP beads	Beckman Coulter	Cat# A63881
ERCC spike-in mix 1	Ambion	Cat# 4456740
16%-Paraformaldehyde Aqueous Solution	Nacalai Tesque	Cat# 15710
1M Phosphate Buffer Solution	Muto Pure Chemicals	Cat# 11281
Triton X-100	Nacalai Tesque	Cat# 12967-32
Bovine Serum Albumin	Sigma-Aldrich	Cat# A9647
DAPI solution (1 mg/mL)	Thermo Fisher	Cat# 62248
Sodium Azide	Nacalai Tesque	Cat# 31233-71
L-Glutamic acid monosodium salt hydrate	Sigma-Aldrich	Cat# G5889
Critical commercial assays
Quick-Neuron Excitatory - SeV Kit	Elixirgen Scientific	Cat# EX-SeV
RNeasy Micro Kit (50)	Qiagen	Cat# 74004
Qubit RNA HS Assay	Thermo Fisher	Cat# Q32852
Qubit dsDNA HS Assay	Thermo Fisher	Cat# Q32851
Nextera XT DNA library preparation kit, 96 samples	Illumina	Cat# FC-131-1096
Nextera XT Index Kit v2 Set A (96 indexes, 384 samples)	Illumina	Cat# FC-131-2001
NextSeq 500/550 Mid Output Kit v2.5 (150 Cycles, 75PE)	Illumina	Cat# 20024904
D5000 ScreenTape	Agilent Technologies	Cat# 5067-4626
D5000 Reagents	Agilent Technologies	Cat# 5067-5593
ReverTra Ace qPCR RT Master Mix	Toyobo	Cat# FSQ-201
KOD SYBR qPCR Mix	Toyobo	Cat# QKD-201
PrimeScript RT-PCR Kit	Takara Bio	Cat# RR014A
Deposited data
Raw and analyzed data: scRNA-seq	This Paper	GEO: GSE224751
Broad Institute's human reference genome GRCh38	TOPMed RNA-seq pipeline	https://github.com/broadinstitute/gtex-pipeline/blob/master/TOPMed_RNAseq_pipeline.md
GENCODE 34 annotations	TOPMed RNA-seq pipeline	https://github.com/broadinstitute/gtex-pipeline/blob/master/TOPMed_RNAseq_pipeline.md
CoDex (Cortical Development Expression) dataset	Polioudakis et al., 201927	http://solo.bmap.ucla.edu/shiny/webapp/
BrainSpan developmental transcriptome dataset RNA-Seq Gencode v10 summarized to genes	Li et al., 201828	https://www.brainspan.org/
Experimental models: Cell lines
CIRM iPS cell line CONTROL: no cognitive decline	FCDI	CW50065
Human iPS cell line derived from healthy individual	RIKEN BRC	HPS0381 : 1231A3
Oligonucleotides
TSO AGCAGTGGTATCAACGCAGAGTACATrGrG+G	IDT Picelli et al., 201447	N/A
Oligo-dT30VN AAGCAGTGGTATCAACGCAGAGTACT30VN	IDT Picelli et al., 201447	N/A
ISPCR oligo AAGCAGTGGTATCAACGCAGAGT	IDT Picelli et al., 201447	N/A
TBP (PrimeTime qPCR Primers) Forward: CAG CAA CTT CCT CAA TTC CTT G Reverse: GCT GTT TAA CTT CGC TTC CG	IDT	Hs.PT.58v.39858774
DBN1 all isoforms Forward: CAC GGA GAT CCA CGA TGC AG Reverse: TGC CAG GCC ATA GGT CAA TGA G	IDT Togo et al., 20216	N/A
DBN1 isoform A Forward: TTC ATA AAG GCA TCG GAC AGT GG Reverse: ATG GGA GGG AGG AAG AGA GGT TTG G	IDT Togo et al., 20216	N/A
GAPDH Forward: CCA CTT TGT CAA GCT CAT TTC CT Reverse: TCT CTT CCT CTT GTG CTC TTG CT	IDT Togo et al., 20216	N/A
GRIN2B (PrimeTime qPCR Primers) Forward: CTC TCT GTG CTG CCG TTG Reverse: CTT AGC TGC CTT CAT GAT CCA	IDT	Hs.PT.58.26188572
GRIN2B (PrimeTime qPCR Primers) Forward: CCA TGG ATG CAG CTG TAG ATA C Reverse: CAG TTC CGA CAT TGC TTT ATG G	IDT	Hs.PT.58.20804834
GRIN2A (PrimeTime qPCR Primers) Forward: ACG ATG CTG AGA TGG TTG TC Reverse: CTG GTG GTG ATT GTG CTG AA	IDT	Hs.PT.58.2281813
GRIN1 (PrimeTime qPCR Primers) Forward: GTG GAT GGC TAA CTA GGA TGG Reverse: CTC CTG GAA GAT TCA GCT CAA	IDT	Hs.PT.58.39141804
GRIN2A (PrimeTime qPCR Primers) Forward: GCA GAA ACA ATG AGC AGC ATC Reverse: CAA GAA GTA ATG GCA CCG TCT	IDT	Hs.PT.58.26949410
GRIN2B (PrimeTime qPCR Primers) Forward: CAT CAC AAA CAT CAT CAC CCA TAC Reverse: CTT CAT AGA GAC AGG CAT CAG T	IDT	Hs.PT.58.40419546
DBN1 (for semi-quantitative RT-PCR) Forward: ATT GCC CAG CGG CCT GAC AAC CCA AGG GAG Reverse: TCT GCC AGG GTG ACC TCA GTA CCC GAG GGT G	Hiroyuki Yamazaki, Gunma University spikar@gunma-u.ac.jp	N/A (provided as a gift)
Software and algorithms
PRINSEQ++ (v1.2)	Ho and Patrizi, 202148	https://github.com/Adrian-Cantu/PRINSEQ-plus-plus
HISAT2 (v2.1.0)	Kim et al., 201949	https://github.com/DaehwanKimLab/hisat2
StringTie (v2.0.6)	Kovaka et al., 201950	https://github.com/gpertea/stringtie
R version 4.1.0 (2021-05-18)	The R Project for Statistical Computing	https://www.r-project.org/; RRID: SCR_001905
ClusterProfiler	Yu et al., 201251	https://guangchuangyu.github.io/software/clusterProfiler/
Prism 7	GraphPad Software	https://www.graphpad.com/scientific-software/prism/
CellPathfinder (for the CQ1 confocal system)	Yokogawa Electric Corporation	https://www.yokogawa.com/solutions/products-platforms/life-science/high-content-analysis/analysis-software/cellpathfinder/
MaxLab Live Software (for the MaxTwo Multiwell HD-MEA platform)	Maxwell Biosystems	https://www.mxwbio.com/products/maxone-mea-system-microelectrode-array/maxlab-live-software/
Other
NextSeq 500 System	Illumina	Cat# SY-415-1001
Agilent 4200 TapeStation	Agilent Technologies	Cat# G2991BA
Qubit 3.0 Fluorometer	Thermo Fisher	Cat# Q33216
BZ-X800 Microscope	Keyence	https://www.keyence.com/products/microscope/fluorescence-microscope/bz-x700/
CQ1 Confocal System	Yokogawa Electric Corporation	https://www.yokogawa.com/solutions/products-platforms/life-science/high-content-analysis/cellvoyager-cq1/
QuantStudio 12 K Flex System	Thermo Fisher	https://www.thermofisher.com/jp/ja/home/life-science/pcr/real-time-pcr/real-time-pcr-instruments/quantstudio-systems/models/quantstudio-12-flex.html
MaxTwo Multiwell HD-MEA platform	Maxwell Biosystems	https://www.mxwbio.com/products/maxtwo-multiwell-microelectrode-array/
E-Gel EX Agarose Gels, 1%	Thermo Fisher	Cat# G401001
96-well Cell Culture Plates	Eppendorf	Cat# 0030 730.135
96-well Low attachment U-bottom plates	Greiner	Cat# 650970