GEO series

A cross-disease human microglial framework identifies disease-enriched subsets and tool compounds for microglial polarization.

GSE202556 Homo sapiens (human) Single-cell RNA-seq 12 samples Submitted 2024/10/18 Platform GPL24676

At a glance

Single-cell RNA-seq · human · 12 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: Homo sapiens (human)
Samples: 12 samples: 3 × Camptothecin vs 3 × Control vs 3 × Narciclasine vs 3 × Torin2Groups 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: A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial statesNature neuroscience · 2024

Summary (written by the submitters)

Human microglia play a pivotal role in neurological diseases, but few targeted therapies that directly modulate microglial state or function exist due to an incomplete understanding of microglial heterogeneity. We use single-cell RNA sequencing to profile live human microglia from autopsies or surgical resections across diverse neurological diseases and central nervous system regions.

Read the full summary ↓

We observe a central divide between oxidative and heterocyclic metabolism and identify subsets associated with antigen presentation, motility, and proliferation. Specific subsets are enriched in susceptibility genes for neurodegenerative diseases or the disease-associated microglial signature. We validate subtypes in situ with an RNAscope-immunofluorescence pipeline and leverage our dataset as a classification resource, finding that iPSC model systems recapitulate substantial in vivo heterogeneity. Finally, we identify and validate candidates for chemically inducing subtype-specific states in vitro, showing that Camptothecin downregulates the transcriptional signature of disease-enriched subsets and upregulates a signature previously shown to be depleted in Alzheimer’s.

Published in

A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states

Tuddenham JF, Taga M, Haage V et al. · Nature neuroscience 2024 · PMID 39406950 · doi:10.1038/s41593-024-01764-7

This dataset

Open GSE202556 in finder → Find more human 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 GSE202556_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 PRJNA836550 and SRA study SRP374376. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39406950) ↗

Study design

3 × Camptothecin vs 3 × Control vs 3 × Narciclasine vs 3 × Torin2

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM6124410 Camptothecin biological replicate 1 Camptothecin
GSM6124411 Camptothecin biological replicate 2 Camptothecin
GSM6124412 Camptothecin biological replicate 3 Camptothecin
GSM6124413 Control biological replicate 1 Control
GSM6124414 Control biological replicate 2 Control
GSM6124415 Control biological replicate 3 Control
GSM6124416 Narciclasine biological replicate 1 Narciclasine
GSM6124417 Narciclasine biological replicate 2 Narciclasine
GSM6124418 Narciclasine biological replicate 3 Narciclasine
GSM6124419 Torin2 biological replicate 1 Torin2
GSM6124420 Torin2 biological replicate 2 Torin2
GSM6124421 Torin2 biological replicate 3 Torin2

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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.