GEO series

TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism

GSE271074 Mus musculus (mouse) RNA-seq (gene expression) 23 samples Submitted 2025/12/01 Platform GPL21626

At a glance

RNA-seq (gene expression) · mouse · 23 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 23 samples: 5 conditions, mostly with about 4 replicates eachGroups 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: TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonismNature communications · 2026

Summary (written by the submitters)

Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and sequence variants are major risk factors for late onset Alzheimer’s disease (LOAD). Using a reporter model, we observed a gradual upregulation of TREM2 with increasing plaque proximity. Isolated microglia were sorted based on reporter expression, to determine fluorodeoxyglucose (FDG) uptake and the metabolomic, lipidomic, and transcriptomic signatures.

Read the full summary ↓

Uptake of FDG correlated with the gradual increase of TREM2 expression. TREM2 expression improved cellular redox, energetics, and cholesterol homeostasis in the presence or absence of amyloid pathology. Bulk RNA sequencing analysis identified major changes in immunometabolic pathways. Genes associated with oxidative phosphorylation or cholesterol homeostasis were enriched in the TREM2 high expressing clusters. Finally, chronic treatment with a brain penetrant TREM2 agonist identified a window of TREM2 expression where microglia are most accessible for protective responses providing important information for the current efforts to bring TREM2 agonists into the clinic.

Published in

TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism

Feiten AF, Dahm K, Schlepckow K et al. · Nature communications 2026 · PMID 41580393 · doi:10.1038/s41467-026-68706-8

This dataset

Open GSE271074 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 GSE271074_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1129559 and SRA study SRP516852. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41580393) ↗

Study design

5 conditions, mostly with about 4 replicates each

low_healthy ×5 low_disease ×5 mid_healhty ×4 mid_disease ×4 high_disease ×4 mid_healthy ×1

Supports a case/control comparison: 13 samples read as cases, 6 as controls.

How we read this: 5 replicated groups read from 23 sample titles; they account for 22 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

GSM8368232 low_healthy_1 low_healthy
GSM8368233 mid_healhty_1 mid_healhty
GSM8368234 low_healthy_2 low_healthy
GSM8368235 mid_healhty_2 mid_healhty
GSM8368236 low_healthy_3 low_healthy
GSM8368237 mid_healhty_3 mid_healhty
GSM8368238 low_healthy_4 low_healthy
GSM8368239 mid_healhty_4 mid_healhty
GSM8368240 low_healthy_5 low_healthy
GSM8368241 mid_healthy_5
GSM8368242 low_disease_1 low_disease
GSM8368243 mid_disease_1 mid_disease
GSM8368244 low_disease_2 low_disease
GSM8368245 mid_disease_2 mid_disease
GSM8368246 high_disease_2 high_disease
GSM8368247 low_disease_3 low_disease
GSM8368248 mid_disease_3 mid_disease
GSM8368249 high_disease_3 high_disease
GSM8368250 low_disease_4 low_disease
GSM8368251 high_disease_4 high_disease
GSM8368252 low_disease_5 low_disease
GSM8368253 mid_disease_5 mid_disease
GSM8368254 high_disease_5 high_disease

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