GEO series

Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease [RNA-seq]

GSE288504 Mus musculus (mouse) Single-cell RNA-seq 15 samples Submitted 2025/04/30 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 15 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: 15 samples: 6 conditions, mostly in triplicateGroups 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: Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological diseaseImmunity · 2025

Summary (written by the submitters)

Krabbe disease, also named Globoid Cell Leukodystrophy (GLD) for its distinct lipid- laden macrophages, is a severe leukodystrophy caused by galactosylceramidase (GALC) mutations. Hematopoietic stem cell transplant (HSCT) ameliorates disease and is associated with central nervous system (CNS) engraftment of GALC+ donor macrophages. Yet, the role of macrophages in GLD pathophysiology and HSCT remains unclear.

Read the full summary ↓

Using single-cell sequencing we revealed early interferon response signatures which precede progressively severe macrophage dyshomeostasis, and identified a molecular signature of globoid cells, which we validated in human brain specimens. Genetic depletion and direct microglia replacement by CNS monocyte injection rapidly replaced >80% of endogenous microglia with healthy monocytes in the twitcher (GalcW355*) mouse, a faithful model of GLD. Perinatal microglia replacement completely normalized transcriptional signatures, rescued histopathology, and doubled average survival. Overall, we uncovered distinct forms of microglia dysfunction, and evidence that direct, CNS-limited microglia replacement improves a monogenic neurodegenerative disease, a promising therapeutic target.

Published in

Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease

Aisenberg WH, O'Brien CA, Sangster M et al. · Immunity 2025 · PMID 40311614 · doi:10.1016/j.immuni.2025.03.019

This dataset

Open GSE288504 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 GSE288504_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 PRJNA1217888 and SRA study SRP560922. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40311614) ↗

Study design

6 conditions, mostly in triplicate

twitcher, myeloid, P10, sample ×3 twitcher, myeloid, P20, sample ×3 WT, myeloid, P20, sample ×3 WT, myeloid, P10, sample ×2 twitcher, myeloid, P15, sample ×2 WT, myeloid, P15, sample ×2

Supports a between-group comparison across 15 samples.

How we read this: 6 replicated groups read from 15 sample titles; they account for 15 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

GSM8769122 twitcher, myeloid, P10, sample1 twitcher, myeloid, P10,…
GSM8769123 twitcher, myeloid, P10, sample2 twitcher, myeloid, P10,…
GSM8769124 twitcher, myeloid, P10, sample3 twitcher, myeloid, P10,…
GSM8769125 WT, myeloid, P10, sample1 WT, myeloid, P10, sample
GSM8769126 WT, myeloid, P10, sample2 WT, myeloid, P10, sample
GSM8769127 twitcher, myeloid, P15, sample1 twitcher, myeloid, P15,…
GSM8769128 twitcher, myeloid, P15, sample2 twitcher, myeloid, P15,…
GSM8769129 WT, myeloid, P15, sample1 WT, myeloid, P15, sample
GSM8769130 WT, myeloid, P15, sample2 WT, myeloid, P15, sample
GSM8769131 twitcher, myeloid, P20, sample1 twitcher, myeloid, P20,…
GSM8769132 twitcher, myeloid, P20, sample2 twitcher, myeloid, P20,…
GSM8769133 twitcher, myeloid, P20, sample3 twitcher, myeloid, P20,…
GSM8769134 WT, myeloid, P20, sample1 WT, myeloid, P20, sample
GSM8769135 WT, myeloid, P20, sample2 WT, myeloid, P20, sample
GSM8769136 WT, myeloid, P20, sample3 WT, myeloid, P20, sample

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