Key resources table
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Rabbit polyclonal anti-MAP2 | Cell Signaling Technology | Cat# 4542S; RRID: AB_ 10693782 |
| Rabbit polyclonal anti-MAP2 | Millipore | Cat# AB5622; RRID: AB_91939 |
| Rabbit polyclonal anti-Tau | Aligent/Dako | Cat# 002401-2; RRID: AB_10013724 |
| Mouse monoclonal anti-TUBB3 | BioLegend | Cat# 801202; RRID: AB_ 10063408 |
| Rabbit polyclonal anti-TUBB3 | BioLegend | Cat# 802001, RRID: AB_2564645 |
| Chicken polyclonal anti-TUBB3 | Novus | Cat# NB100-1612, RRID: AB_10000548 |
| Mouse monoclonal anti-Tau (CP-27) | Peter Davies, Albert Einstein College of Medicine | Cat# CP-27; RRID: AB_2716722 |
| Mouse monoclonal anti-Tau (Tau1) | Nicholas M. Kanaan, Michigan State University | Cat# Tau1; RRID: AB_2721197 |
| Mouse monoclonal anti-Tau (HJ8.5) | David Holtzman, Washington University in St. Louis | Cat# HJ8.5; RRID: AB_2721237 |
| Mouse monoclonal anti-NCAM1 | Santa Cruz Biotechnology | Cat#SC-106; RRID: AB_627128 |
| Mouse monoclonal anti-pTau (AT8) | Thermo Fisher Scientific | Cat# MN1020; RRID: AB_223647 |
| Mouse monoclonal anti-pTau (CP13) | Peter Davies, Albert Einstein College of Medicine | Cat# CP13; RRID: AB_2314223 |
| Mouse monoclonal anti-conformationally abnormal Tau (MC1) | Peter Davies, Albert Einstein College of Medicine | Cat# MC1; RRID: AB_2314773 |
| Mouse monoclonal anti-pTau (PHF1) | Peter Davies, Albert Einstein College of Medicine | Cat# PHF1; RRID: AB_2315150 |
| Mouse monoclonal anti-oligomeric Tau (TOC1) | Nicholas M. Kanaan, Michigan State University | Cat# TOC1; RRID: AB_2832939 |
| Rabbit polyclonal anti-Neurofilament Heavy Chain | Abcam | Cat# ab8135; RRID: AB_306298 |
| Abberior StarRed goat anti-mouse | Abberior | Cat# STRED-1001-500UG |
| Biological samples | ||
| Fetal Brain RNA– Fbrain 1 | Tebu Bio | 1F01-50 |
| Fetal Primary Neurons – FPN 1 | ScienCell | 1520 |
| Fetal Primary Neurons – FPN 2 | ScienCell | 1520 |
| Fetal Primary Neurons – FPN 3 | ScienCell | 1520 |
| iPSC-derived cortical neurons – iPSC-CN 1 | BrainXell | BX-0300 |
| Fetal neuron lysate – FNL 1 | ScienCell | 1526 |
| Adult Brain RNA, Male 29yr - ABrain 1 | BioChain | R1234066-50 |
| Adult Brain RNA, Male 66yr - ABrain 2 | BioChain | R1234066-50 |
| Adult Brain RNA, Female 78yr - ABrain 3 | BioChain | R1234066-50 |
| Adult Brain RNA, Male 82yr - ABrain 4 | NovusBio | NB820-59177 |
| Adult Brain Lysate, Male 90yrs - ABrain 5 | Dr. Chihiro Sato, Washington University in Saint Louis | n/a |
| Adult Brain Lysate, Male 80yrs - ABrain 6 | Dr. Chihiro Sato, Washington University in Saint Louis | n/a |
| Adult Brain Lysate, Male 87yrs - ABrain 7 | Dr. Chihiro Sato, Washington University in Saint Louis | n/a |
| Adult Brain Lysate, Male 72yrs - ABrain 8 | Dr. Chihiro Sato, Washington University in Saint Louis | n/a |
| IVS10+16 Adult Brain RNA, Male 66rs – IVS10+16 ABrain | Queen Square House Brain Bank | P2/08 |
| Chemicals, peptides, and recombinant proteins | ||
| Fetal bovine serum (FBS), qualified, US Department of Agriculture (USDA)-approved regions | Life Technologies | Cat# 10437028 |
| Polybrene | Sigma-Aldrich | Cat# H9268 |
| Neurobasal-A | Gibco | Cat# 10888022 |
| GlutaMAX | Gibco | Cat# 35050061 |
| B27 Plus Supplement | Gibco | Cat# A3582801 |
| BrainPhys Neuronal Medium | StemCell | Cat# 05790 |
| NeuroCult SM1 Neuronal Supplement | StemCell | Cat# 05711 |
| N2 Supplement-A | StemCell | Cat# 07152 |
| Doxycycline hyclate (Dox) | Sigma-Aldrich | Cat# D9891 |
| Poly-L-ornithine solution | Sigma-Aldrich | Cat# P4957 |
| Laminin | Sigma-Aldrich | Cat# L2020 |
| Fibronectin | Sigma-Aldrich | Cat# F4759 |
| Valproic acid (VPA), sodium salt | Sigma-Aldrich | Cat# 676380 |
| Dibutyryl-cAMP sodium salt | Sigma-Aldrich | Cat# D0627 |
| Retinoic acid (RA) | Sigma-Aldrich | Cat# R2625 |
| Neurotrophin-3 (NT-3) | PeproTech | Cat# 450-03 |
| Brain-derived neurotrophic factor (BDNF) | PeproTech | Cat# 450-02 |
| Glial-derived Neurotrophic Factor (GDNF) | PeproTech | Cat# 450-10 |
| RevitaCell Supplement | Thermo Fisher Scientific | Cat# A2644501 |
| ISX-9 | StemCell Technologies | Cat# 73202 |
| DAPT | Millipore Sigma | Cat# D5942 |
| Critical commercial assays | ||
| Go Taq DNA Polymerase | Promega | Cat# M3001 |
| RNeasy Plus Micro Kit | QIAGEN | Cat# 74034 |
| SMARTer Ultra Low RNA Kit for Illumina sequencing | Clontech | Cat# 635029 |
| TruSeq Small RNA Library Preparation Kit | Illumina | Cat# RS-200-0012 |
| ReliaPrep™ RNA Miniprep Systems | Promega | Cat# Z6011 |
| QIAamp DNA Mini Kit | QIAGEN | Cat# 51304 |
| QIAquick Gel Extraction Kit | QIAGEN | Cat# 28706 |
| Deposited data | ||
| Raw and processed data (Single-cell RNA-sequencing, bulk RNA-sequencing) | NCBI Gene Expression Omnibus | Accession #: GSE201084 |
| Western Blot | Mendeley Data | DOI: 10.17632/t93byrznm6.1 |
| Experimental models: Cell lines | ||
| Lenti-X 293LE cell line | Clontech | Cat# 632180 |
| AG04148, Male 56yrs – Control 1 | Coriell | Cat# AG04148 |
| AG08260, Male 61yrs – Control 2 | Coriell | Cat# AG08260 |
| AG08379, Female 60yrs – Control 3 | Coriell | Cat# AG08379 |
| AG13369, Male 68yrs – Control 4 | Coriell | Cat# AG13369 |
| UCL455, Male 53yrs – IVS10+16 1 | Dr.Henry Houlden, University College London | n/a |
| UCL457, Male 52yrs – IVS10+16 2 | Dr.Henry Houlden, University College London | n/a |
| UCL497, Female 54yrs – IVS10+16 3 | Dr.Henry Houlden, University College London | n/a |
| ES046, Male 57yrs – IVS10+16 4 | Dr. Barbara Corneo, Columbia University | n/a |
| Oligonucleotides | ||
| Primers for qPCR; see Table S3 | This paper | n/a |
| Primers for sqPCR; see Table S3 | This paper | n/a |
| Primers for sequencing; see Table S3 | This paper | n/a |
| Recombinant DNA | ||
| pMD2.G | Didier Trono | 12259 |
| psPAX2 | Didier Trono | 12260 |
| rtTA-N144 | Richner et al., 2015 | 66810 |
| pTight-9/9*-124-Bclxl | Victor et al., 2014 | 60857 |
| MYT1L-N174 | Richner et al., 2015 | 66809 |
| Software and algorithms | ||
| ImageJ | Schneider et al., 2012 | https://imagej.nih.gov/ij/ |
| LAS X | Leica Microsystems | https://www.leica-microsystems.com/products/microscope-software/p/leica-las-x-ls/ |
| Harmony v4.9 | Perkin Elmer | https://www.perkinelmer.com/product/harmony-4-8-office-hh17000001 |
| Graphpad Prism 9 | GraphPad Software Inc | http://www.graphpad.com/ |
| FCS Express 7 Research software | De Novo Software | https://denovosoftware.com/ |
| Ingenuity Pathway Analysis | QIAGEN | https://digitalinsights.qiagen.com/products-overview/discovery-insights-portfolio/analysis-and-visualization/qiagen-ipa/ |
| Skyline | MacCoss Lab Software, MacLean et al., 2010 | https://skyline.ms/project/home/software/Skyline/begin.view |
| Cell Ranger (v3.1.0) | 10x Genomics, Zheng et al., 2017 | https://support.10xgenomics.com/single-cell-gene-expression/software/pipelines/latest/what-is-cell-ranger |
| Seurat (v3.2.3) | Santija Lab, Satija et al., 2015 | https://satijalab.org/seurat/ |
| Cutadapt v2.4 | Martin, 2011; National Bioinformatics Infrastructure Sweden | https://github.com/marcelm/cutadapt/ |
| DESeq2 | Love, Huber, and Anders, 2014 | https://bioconductor.org/packages/release/bioc/html/DESeq2.html |
| FastQC v0.11.4 | Simon Andrews, 2010 | https://www.bioinformatics.babraham.ac.uk/projects/fastqc/ |
| Deeptools (v3.5.1) | Ramirez et al., 2014 | http://deeptools.ie-freiburg.mpg.de |
| Wiggletools (v1.2) | Zerbino et al., 2014 | www.github.com/Ensembl/Wiggletools |
| Samtools v1.9 | Li et al., 2009 | http://samtools.sourceforge.net/ |
| Picard v2.18 | Broad Institute | https://broadinstitute.github.io/picard/ |
| IGV | Thorvaldsdóttir et al., 2013 | https://software.broadinstitute.org/software/igv/download |
| STAR | Dobin et al., 2015 | https://github.com/alexdobin/STAR |
| LONGO | McCoy et al., 2018 | https://github.com/biohpc/longo |
| Leafcutter | Li et al., 2018 | https://davidaknowles.github.io/leafcutter/ |