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Series GSE129308 Query DataSets for GSE129308
Status Public on Aug 05, 2020
Title Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Tau aggregation in neurofibrillary tangles (NFTs) is closely associated with neurodegeneration and cognitive decline in Alzheimer’s disease (AD). However, the molecular signatures that distinguish between aggregation-prone and aggregation-resistant cell states are unknown. We developed methods for the high-throughput isolation and transcriptome profiling of single somas with NFTs fro¬m human AD brain, quantified the susceptibility of 20 neocortical subtypes for NFT formation and death, and identified both shared and cell-type-specific signatures. NFT-bearing neurons shared a marked upregulation of synaptic transmission-related genes, including a core set of 63 genes enriched for synaptic vesicle cycling. Oxidative phosphorylation and mitochondrial dysfunction were highly cell-type dependent. Apoptosis was only modestly enriched, and the susceptibilities of NFT-bearing and NFT-free neurons for death were highly similar. Our analysis suggests that NFTs represent cell-type-specific responses to stress and synaptic dysfunction. We provide a resource for biomarker discovery and the investigation of tau-dependent and tau-independent mechanisms of neurodegeneration.
Overall design Fresh frozen brain tissue from the prefrontal cortex (BA9) of eight Braak stage VI AD and eight age-matched healthy control donors was micro-dissected and dissociated without detergents or enzymatic digestion. Immunostaining and FACS using an antibody to detect pathological tau aggregates (AT8) and the pan-neuronal marker MAP2 was used to isolate somas with NFTs (n = 24,660) and neighboring NFT-free neurons (n = 38,465) from AD donors and control NFT-free somas (n = 63,110). RNA capture and library preparation was performed using the 10× Genomics Chromium Single Cell 3’ v2 or v3 assay. The generated paired-end libraries were sequenced on Illumina Novaseq 6000. Paired-end sequence reads were processed using the 10× Genomics software package Cell Ranger and the R-based Seurat package. Raw data is available in SRA with Study accession SRP189891 and Bioproject accession PRJNA528824.
Web link
Contributor(s) Otero-Garcia M, Xue Y, Shakouri T, Deng Y, Morabito S, Kawaguchi R, Swarup V, Cobos I
Citation Marcos Otero-Garcia, Yue-Qiang Xue, Tamara Shakouri, Yongning Deng, Samuel Morabito, Thomas Allison, William E. Lowry, Riki Kawaguchi, Vivek Swarup, Inma Cobos. Single-soma transcriptomics of tangle-bearing neurons in Alzheimer's disease reveals the signatures of tau-associated synaptic dysfunction. bioRxiv 2020.05.11.088591; doi:10.1101/2020.05.11.088591.
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 AG059848 Resolving selective vulnerability and disease progression in human Alzheimer's brain via single-cell RNA-seq STANFORD UNIVERSITY Maria Inmaculada Cobos Sillero
Submission date Apr 03, 2019
Last update date Nov 29, 2022
Contact name Inma Cobos
Phone 6507258200
Street address 300 Pasteur Drive, Lane Building, L235
City Stanford
State/province California
ZIP/Postal code 94305-5324
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (27)
GSM3704357 1-MAP2
GSM3704358 1-AT8
GSM3704359 2-MAP2
BioProject PRJNA530780
SRA SRP190819

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Supplementary file Size Download File type/resource
GSE129308_RAW.tar 321.0 Mb (http)(custom) TAR (of H5)
GSE129308_Sequencing_metrics.csv.gz 1.6 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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