GEO series

Microglia contribute to polyG-dependent neurodegeneration in neuronal intranuclear inclusion disease II

GSE269183 Mus musculus (mouse) Single-nucleus RNA-seq 16 samples Submitted 2024/07/04 Platform GPL24247

At a glance

Single-nucleus RNA-seq · mouse · 16 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 16 samples: 4 × Cx-3A6 vs 4 × Cx-3A7 vs 4 × Cx-3A8 vs 4 × Cx-3A9Groups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Microglia contribute to polyG-dependent neurodegeneration in neuronal intranuclear inclusion diseaseActa neuropathologica · 2024

Summary (written by the submitters)

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease caused by GGC repeat expansion of NOTCH2NLC. Despite the identification of uN2CpolyG, a toxic polyglycine (polyG) protein, the pathogenic mechanisms of NIID remain unclear. Herein, we investigated the role of polyG by expressing wild-type NOTCH2NLC, expanded NOTCH2NLC with 100 GGC repeats (translating or not translating into uN2CpolyG), or mutated NOTCH2NLC that encodes a pure polyG without GGC-repeat RNA and C-terminal stretch (uN2CpolyG-dCT) in mice.

Read the full summary ↓

Both uN2CpolyG and uN2CpolyG-dCT induced the formation of inclusions composed by filamentous materials and caused neurodegenerative phenotypes in mice, including impaired motor and cognitive performance, shortened lifespan, and pathological lesions such as white matter lesions, microgliosis, and astrogliosis. By contrast, the sole expression of GGC-repeat RNA was non-pathogenic. Combining with bulk and single-nuclei RNA-seq, we determined the common molecular signatures associated with expressing uN2CpolyG and uN2CpolyG-dCT in the brain, especially the up-regulation of inflammation and microglia markers whereas down-regulation of immediate early genes and splicing factors. Importantly, microglia-mediated inflammation was visualized in NIID patients by positron emission tomography, which correlated with white matter atrophy levels. Moreover, microglia ablation ameliorated neurodegeneration in uN2CpolyG-expressing mice but did not alter polyG inclusions. Together, these results demonstrate that polyG is critical for the pathogenesis of NIID, and microglia contribute to polyG-induced neurodegeneration.

Published in

Microglia contribute to polyG-dependent neurodegeneration in neuronal intranuclear inclusion disease

Zhong S, Lian Y, Zhou B et al. · Acta neuropathologica 2024 · PMID 39150562 · doi:10.1007/s00401-024-02776-0

This dataset

Open GSE269183 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE269183_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1120470 and SRA study SRP512045. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39150562) ↗

Study design

4 × Cx-3A6 vs 4 × Cx-3A7 vs 4 × Cx-3A8 vs 4 × Cx-3A9

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8307726 Cx-3A6-1 Cx-3A6
GSM8307727 Cx-3A6-2 Cx-3A6
GSM8307728 Cx-3A6-3 Cx-3A6
GSM8307729 Cx-3A6-4 Cx-3A6
GSM8307730 Cx-3A7-1 Cx-3A7
GSM8307731 Cx-3A7-2 Cx-3A7
GSM8307732 Cx-3A7-3 Cx-3A7
GSM8307733 Cx-3A7-4 Cx-3A7
GSM8307734 Cx-3A8-1 Cx-3A8
GSM8307735 Cx-3A8-2 Cx-3A8
GSM8307736 Cx-3A8-3 Cx-3A8
GSM8307737 Cx-3A8-4 Cx-3A8
GSM8307738 Cx-3A9-1 Cx-3A9
GSM8307739 Cx-3A9-2 Cx-3A9
GSM8307740 Cx-3A9-3 Cx-3A9
GSM8307741 Cx-3A9-4 Cx-3A9

Datasets on a similar topic

GSE295763 Precise Excision of Expanded GGC Repeats in NOTCH2NLC via CRISPR/Cas9 for Treating Neuronal Intranuclear Inclusion Disease 18 samples shares intranuclear, inclusion, neuronal
GSE263679 Integrated stress response associated with dark microglia contributes to neurodegeneration [TRAP-seq] 29 samples shares neurodegeneration, contribute, microglia
GSE254104 Alzheimer’s disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model [snRNAseq] 27 samples shares neurodegeneration, microglia
GSE254103 Alzheimer’s disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model [bulk_RNAseq] 24 samples shares neurodegeneration, microglia
GSE291086 Neuronal ABCA7 deficiency aggravates mitochondrial dysfunction and neurodegeneration in Alzheimer’s disease 24 samples shares neurodegeneration, neuronal
GSE254996 ACSS2 upregulation enhances neuronal resilience to aging and neurodegeneration [RNA-seq] 98 samples shares neurodegeneration, neuronal
GSE247436 Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model 32 samples shares neurodegeneration, microglia
GSE304931 Alpha retinal ganglion cell-derived SPP1 instructs microglia to limit neurodegeneration 23 samples shares neurodegeneration, microglia

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.