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Microglia regulate cortical remyelination via ΤNFR1-dependent phenotypic polarization [RNA-Seq]

GSE278137 Mus musculus (mouse) Single-cell RNA-seq 28 samples Submitted 2024/11/12 Platform GPL21626
At a glance

Single-cell RNA-seq · mouse · 28 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. 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
28 samples: 7 × Whole brain, TNFR1ff, demyelination, vs 7 × Whole brain, mgTNFR1KO, remyelination, vs 7 × Whole brain, TNFR1ff, naive, vs 7 × Whole brain, TNFR1ff, remyelination,Groups 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 regulate cortical remyelination via TNFR1-dependent phenotypic polarizationCell reports · 2024
Summary (written by the submitters)
Microglia are strongly implicated in demyelinating neurodegenerative diseases with increasing evidence for roles in protection and healing, but the mechanisms that control CNS remyelination are poorly understood. Here we show that microglia-specific deletion of TNFR1 and pharmacological inhibition of soluble TNF (solTNF) or downstream IL-1R allow maturation of highly activated disease-associated microglia with increased size and myelin phagocytosis capacity that accelerate cortical remyelination and motor recovery.
Read the full summary ↓
Single cell transcriptomic analysis of cortex at disease onset reveal that solTNF inhibition enhances reparative IL-10-responsive, while preventing damaging IL-1-related signatures of disease-associated microglia. Longitudinal brain transcriptome analysis through disease reveal earlier recovery upon therapeutic loss of microglia TNFR1. Functional relevance of microglia inflammatory polarization pathways for disease is validated in vivo. Furthermore, disease-state microglia producing downstream IL-1/IL-18/NLRP3/CASP1 targets are identified in human demyelinating lesions. Overall, redirecting disease microglia polarization by targeting cytokines is a potential approach for improving CNS repair in demyelinating disorders.
Published in
Microglia regulate cortical remyelination via TNFR1-dependent phenotypic polarization
Boutou A, Roufagalas I, Politopoulou K et al. · Cell reports 2024 · PMID 39446583 · doi:10.1016/j.celrep.2024.114894
This dataset
Open GSE278137 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 GSE278137_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 PRJNA1165754 and SRA study SRP535015. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39446583) ↗
Study design
7 × Whole brain, TNFR1ff, demyelination, vs 7 × Whole brain, mgTNFR1KO, remyelination, vs 7 × Whole brain, TNFR1ff, naive, vs 7 × Whole brain, TNFR1ff, remyelination,

Supports a between-group comparison across 28 samples.

How we read this: 4 replicated groups read from 28 sample titles; they account for 28 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
Datasets on a similar topic

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