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CNS infiltration by Tet2-mutant peripheral myeloid cells protects from Alzheimer’s Disease

GSE298597 Mus musculus (mouse) Single-cell RNA-seq 12 samples Submitted 2025/06/06 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 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
Mus musculus (mouse)
Samples
12 samples: 6 conditions, mostly in duplicateGroups 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
TET2-mutant myeloid cells mitigate Alzheimer's disease progression via CNS infiltration and enhanced phagocytosis in miceCell stem cell · 2025
Summary (written by the submitters)
Bone marrow-derived peripheral immune cells have been found to infiltrate the brain in many neurodegenerative diseases, such as Alzheimer's disease (AD). Using a mouse transplant model of AD (5xFAD mice), we found that loss of the clonal hematopoiesis associated gene Tet2 within peripheral immune cells led to increased myeloid cell brain infiltration when compared to mice with either wildtype or Dnmt3a-mutant peripheral immune cells.
Read the full summary ↓
scRNA-seq on either CD11a-enriched or CD45-enriched brain cells from 5xFAD mice transplanted with either wildtype, Tet2-/- or Dnmt3a-/- bone marrow, confirmed our finding that loss of Tet2 leads to increased peripheral myeloid cell brain infiltration in AD mice. scRNA-seq identified that the change in infiltrating peripheral immune cells was primarily attributed to increased M1 macrophages and non-classical monocytes in the brains of 5xFAD mice with Tet2-mutant bone marrow. We further identified the upregulation of chemotaxis and migration related pathways in Tet2-mutant infiltrating macrophages and monocytes when compared to wildtype or Dnmt3a-mutant infiltrating cells, providing a mechanism by which loss of Tet2 in peripheral immune cells leads to increased brain infiltration in an AD setting.
Published in
TET2-mutant myeloid cells mitigate Alzheimer's disease progression via CNS infiltration and enhanced phagocytosis in mice
Matatall KA, Wathan TK, Nguyen M et al. · Cell stem cell 2025 · PMID 40609533 · doi:10.1016/j.stem.2025.06.006
This dataset
Open GSE298597 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 GSE298597_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 PRJNA1270000 and SRA study SRP588879. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40609533) ↗
Study design
6 conditions, mostly in duplicate
main, WT Tx 5xFAD, ×2 main, Tet2-/- Tx 5xFAD, ×2 main, Dnmt3a-/- Tx 5xFAD, ×2 validation, WT Tx 5xFAD, ×2 validation, Tet2-/- Tx 5xFAD, ×2 validation, Dnmt3a-/- Tx 5xFAD, ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 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
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