KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Goat polyclonal anti-human progranulin | R&D Systems | Cat#AF2420; RRID:AB_2114489 |
| Mouse monoclonal anti-TUJ1 | BioLegend | Cat#801201; RRID:AB_2313773 |
| Donkey polyclonal anti-goat AF-488 | Jackson ImmunoResearch | Cat#705-545-147; RRID:AB_2336933 |
| Donkey polyclonal anti-mouse RRX | Jackson ImmunoResearch | Cat#715-295-151; RRID:AB_2340832 |
| Donkey polyclonal anti-goat AF-647 | Jackson ImmunoResearch | Cat#705-605-147; RRID:AB_2340437 |
| Donkey polyclonal anti-mouse AF-488 | Jackson ImmunoResearch | Cat#715-545-151; RRID:AB_2341099 |
| Guinea pig polyclonal anti-NeuN | MilliporeSigma | Cat#ABN90; RRID:AB_11205592 |
| Mouse monoclonal anti-human tau | ThermoFisher Scientific | Cat#MN1000; RRID:AB_2314654 |
| Goat polyclonal anti-guinea pig AF-647 | ThermoFisher Scientific | Cat#A-21450; RRID:AB_2735091 |
| Mouse monoclonal anti- β-Actin (8H10D10) | Cell Signaling Technology | Cat# 3700, RRID:AB_2242334 |
| Mouse monoclonal anti- phospho-Histone H2A.X (Ser139) | Millipore | Cat# 05-636, RRID:AB_309864 |
| Rabbit monoclonal anti-UBQLN2 (D7R2Z) | Cell Signaling Technology | Cat# 85509, RRID:AB_2800056 |
| IRDye 680RD Goat anti-Mouse IgG | LI-COR Biosciences | Cat# 926-68070, RRID:AB_10956588 |
| IRDye 800CW Goat anti-Rabbit IgG | LI-COR Biosciences | Cat# 926-32211, RRID:AB_621843 |
| Chemicals, Peptides, and Recombinant Proteins | ||
| Trimethoprim | Sigma | Cat#92131-5G |
| CNQX disodium salt | Tocris | Cat#1045 |
| Puromycin dihydrochloride | Sigma | Cat#P9620-10ML |
| Blastidicin S HCl | Gemini Bio-Products | Cat#400-165P |
| Hoechst 33342 | ThermoFisher Scientific | Cat#62249 |
| DRAQ5 | ThermoFisher Scientific | Cat#62251 |
| Lipofectamine Stem | ThermoFisher Scientific | Cat#STEM00003 |
| Alt-R S.p. HiFi Cas9 Nuclease V3 | IDT | Cat#1081060 |
| Lipofectamine 3000 Transfection Reagent | ThermoFisher Scientific | Cat# L3000015 |
| Lipofectamine 2000 Transfection Reagent | Invitrogen | Cat#11668027 |
| ViralBoost | Alstem | Cat#VB100 |
| Lentivirus Precipitation Solution | Alstem | Cat# VC100 |
| Opti-MEM I Reduced Serum Medium | Gibco | Cat#31985070 |
| BrainPhys Neuronal Medium | STEMCELL Technologies | Cat#05790 |
| BrainPhys without Phenol Red | STEMCELL Technologies | Cat#05791 |
| Cultrex 3D Culture Matrix Laminin I | R&D Systems | Cat#3446-005-01 |
| Doxycycline hyclate | Sigma | Cat#D9891 |
| Poly-L-ornithine hydrobromide | Sigma-Aldrich | Cat#P3655-50MG |
| Etoposide | Abcam | Cat#ab120227 |
| Essential 8 Medium | Thermo Fisher Scientific | Cat#A1517001 |
| Matrigel Basement Membrane Matrix | Corning | Cat#356231 |
| Y-27632 dihydrochloride ROCK inhibitor | Tocris | Cat#125410 |
| N2 Supplement | Thermo Fisher Scientific | Cat#17502-048 |
| B27 Supplement | Thermo Fisher Scientific | Cat#17504-044 |
| NT-3 | PeproTech | Cat#450-03 |
| BDNF | PeproTech | Cat#450-02 |
| Mevastatin | Sigma-Aldrich | Cat#M2537 |
| Laminin Mouse Protein, Natural | ThermoFisher Scientific | Cat#23017-015 |
| Knockout DMEM/F12 | ThermoFisher Scientific | Cat#12660-012 |
| MEM Non-Essential Amino Acids Solution (100X) | ThermoFisher Scientific | Cat#11140-050 |
| GlutaMAX Supplement | ThermoFisher Scientific | Cat#35050-061 |
| Neurobasal-A Medium | ThermoFisher Scientific | Cat#10888-022 |
| StemPro Accutase Cell Dissociation Reagent | ThermoFisher Scientific | Cat# A11105-01 |
| Knockout DMEM | ThermoFisher Scientific | Cat#10829-018 |
| Papain | Worthington Biochemical | Cat# LK003178 |
| DNase I | Worthington Biochemical | Cat# LS006333 |
| 1X Hank’s Balanced Salt Solution | Corning | Cat#21-022-CV |
| DMEM | ThermoFisher Scientific | Cat#10313-039 |
| Mevalonate | Sigma-Aldrich | Cat#M4667 |
| Critical Commercial Assays | ||
| Direct-zol 96 RNA Kit | Zymo | Cat#R2055 |
| iTaq Universal Probes One-Step Kit | Bio-Rad | Cat#172-5141 |
| Chromium Single Cell 3’ Library & Gel Bead Kit v2 | 10x Genomics | Cat# 120267 |
| Chromium i7 Multiplex Kit Kit | 10x Genomics | Cat#120262 |
| Chromium Single Cell A Chip | 10x Genomics | Cat#1000009 |
| Chromium Controller & Accessory Kit | 10x Genomics | Cat#120223 |
| NucleoSpin Blood L Kit | Macherey-Nagel | Cat#740954.20 |
| NucleoSpin Blood XL Kit | Macherey-Nagel | Cat#740950.10 |
| Quick-RNA Miniprep Kit | Zymo | Cat#R1054 |
| Qubit RNA HS Assay Kit | Invitrogen | Cat#Q32855 |
| QuantSeq 3’ mRNA-Seq Library Prep Kit FWD | Lexogen | Cat#015 |
| Qubit dsDNA HS Assay Kit | Invitrogen | Cat#Q32851 |
| High Sensitivity DNA Kit | Agilent | Cat#5067-4626 |
| SensiFAST SYBR Lo-ROX 2X master mix | Bioline | Cat#BIO-94005 |
| GAPDH PrimePCR Primers | Bio-Rad | Unique Assay ID:qHsaCEP0041396 |
| GRN PrimePCR Primers | Bio-Rad | Unique Assay ID:qHsaCEP0057821 |
| UBQLN2 PrimePCR Primers | Bio-Rad | Unique Assay ID:qHsaCEP0055207 |
| Deposited Data | ||
| iNeuron-RNA-Seq | This paper | https://kampmannlab.ucsf.edu/ineuron-rna-seq; GEO: GSE124703 |
| iPSC and Day 7 Neuron CROP-seq Data | This paper | GEO: GSE124703 |
| Experimental Models: Cell Lines | ||
| Human: NCRM5 iPSC line | Luo et al., 2014 | N/A |
| Human: i3N iPSC line | Wang et al., 2017 | N/A |
| Oligonucleotides: Table S4 | ||
| Recombinant DNA | ||
| Plasmid: Ef1a-mNeon-Green-NLS (H53) | This paper | N/A |
| Plasmid: Ef1a-mScarlet (I2) | This paper | N/A |
| Plasmid: Ef1a-GCaMP6m (I1) | This paper | N/A |
| Plasmid: CLYBL-TO-hNGN2-BSD-mApple | Addgene | Addgene Plasmid#124229; RRID:Addgene_124229 |
| Plasmid: pCE-mp53DD | Okita et al., 2013 | Addgene Plasmid#41856; RRID:Addgene_41856 |
| Plasmid: pC13N-CLYBL-CAG-dCas9-BFP-KRAB | This paper | N/A |
| Plasmid: pRT029 | This paper | N/A |
| Plasmid:pMTL3 | This paper | N/A |
| Plasmid:pMTL5 | This paper | N/A |
| Plasmid:pMK1334 | This paper | N/A |
| Software and Algorithms | ||
| NIS Elements AR 5.02.01 64-bit | Nikon Instruments Inc. | https://www.microscope.healthcare.nikon.com/products/software/nis-elements |
| Fiji - 2.0.0-rc-69/1.52n | Schindelin et al., 2012 | https://imagej.net/Fiji |
| CellProfiler- 3.1.5 | Carpenter et al., 2006 | https://cellprofiler.org/ |
| BlueBee Genomics Platform | BlueBee | https://www.bluebee.com/quantseq |
| Bowtie- 1.2.1.1 | Langmead et al., 2009 | http://bowtie-bio.sourceforge.net/index.shtml |
| MAGeCK- 0.5.7 | Lie et al., 2014 | https://sourceforge.net/p/mageck/wiki/Home/ |
| MAGeCK-iNC | This paper | kampmannlab.ucsf.edu/mageck-inc |
| Cell Ranger- 2.2.0 | 10X Genomics | https://support.10xgenomics.com/single-cell-gene-expression/software/pipelines/latest/what-is-cell-ranger |
| R- 3.5.1 | The R project | https://www.r-project.org/ |
| scater- 1.8.4 | McCarthy et al., 2017 | https://bioconductor.org/packages/release/bioc/html/scater.html |
| fgsea – 1.7.1 | Sergushichev, 2016 | https://bioconductor.org/packages/release/bioc/html/fgsea.html |
| WebGestalt | Zhang et al., 2005 | http://www.webgestalt.org/# |
| Cluster- 3.0 | Eisen et al., 1998 | http://bonsai.hgc.jp/~mdehoon/software/cluster/software.htm#ctv |
| Java TreeView- 1.1.6r4 | Saldanha, 2004 | http://jtreeview.sourceforge.net/ |