GEO series

Sequential pathogen exposure normalizes the brain neuroimmune microenvironment and reveals a tissue-resident memory CD8 T cell-microglia axis shaping adult neurogenesis

GSE341988 Mus musculus (mouse) Single-cell RNA-seq 8 samples Submitted 2026/07/31 Platform GPL34328

At a glance

Single-cell RNA-seq · mouse · 8 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: 8 samples: 3 × Uninfected Brain vs 3 × SPExp Brain vs 2 × SPExp CD8 Depleted BrainGroups 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.

Summary (written by the submitters)

T cells are increasingly recognized as long-term residents of the adult brain, where they accumulate with age and exhibit regional diversity. However, the functional consequences of brain T cell residency on CNS microenvironments are not well-understood, particularly in non-aged populations. Conventionally used, young adult Specific Pathogen Free (SPF) mice, exhibit low numbers of T cells in the brain compared to young adult humans, limiting translational relevance.

Read the full summary ↓

In this work we utilize our Specific Pathogen Experienced (SPExp) mouse model, in which prior peripheral microbial exposures lead to significant enrichment of tissue-resident memory (Trm) T cells in the brain, generating a neuroimmune state more closely resembling adult humans. Using this model we recently demonstrated that the presence of resident T cells in the brain influences seizure outcomes in young mice. Here we combined spectral flow cytometry, single-cell RNA sequencing, tissue clearing, behavioral analyses, intravital imaging and blockade strategies to define how CD8 Trm impact brain microenvironment. At immune memory timepoints following peripheral pathogen exposures, SPExp mice exhibited CD8 Trm localization near neurogenic niches in the brain. Sholl analysis of microglia in the vicinity of these neurogenic niche CD8s displayed a more activated phenotype. Intravital imaging demonstrated that CD8 Trm are motile and form sustained contacts with microglia in vivo, corresponding to the changes in activation state. RNAseq identified robust CD8 T cell-dependent transcriptional changes in microglia. Differential expression revealed distinct primed and senescence-associated microglial phenotypes enriched for interferon-signaling, metabolic stress adaptation, and immune surveillance genes and down regulated neuronal support and signaling genes; with reversal of this upon CD8 T cell depletion. Additionally, KEGG/GO analyses suggest induced microglial states downregulate support for neuronal development. Flow and imaging data found neural stem cells (NSCs) were increased in the niches, but proliferation was abrogated. Proliferation of NSCs was restored after CD8 depletion. Together, these findings identify CD8 Trm as key regulators of microglial state and neurogenesic capacity in the brain, establishing a new paradigm for adaptive immune regulation of brain function at homeostasis.

This dataset

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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 GSE341988_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 PRJNA1504957 and SRA study SRP722886. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × Uninfected Brain vs 3 × SPExp Brain vs 2 × SPExp CD8 Depleted Brain

Supports a between-group comparison across 8 samples.

How we read this: 3 replicated groups read from 8 sample titles; they account for 8 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

GSM9921388 Uninfected Brain 1 Uninfected Brain
GSM9921389 Uninfected Brain 2 Uninfected Brain
GSM9921390 Uninfected Brain 3 Uninfected Brain
GSM9921391 SPExp Brain 1 SPExp Brain
GSM9921392 SPExp Brain 2 SPExp Brain
GSM9921393 SPExp Brain 3 SPExp Brain
GSM9921394 SPExp CD8 Depleted Brain 1 SPExp CD8 Depleted Brain
GSM9921395 SPExp CD8 Depleted Brain 2 SPExp CD8 Depleted Brain

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