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Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD

GSE250280 Homo sapiens (human) Single-nucleus RNA-seq 39 samples Submitted 2025/06/30 Platform GPL24247Platform GPL24676
At a glance

Single-nucleus RNA-seq · human · 39 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). 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
39 samples: 7 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
Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTDCommunications biology · 2025
Summary (written by the submitters)
Genetic mutations in the progranulin gene, GRN, cause frontotemporal dementia and a lysosomal storage disorder. Using single-nuclei RNA sequencing of the post-mortem brain tissue from heterozygous pathogenic granulin variant (GRN+/-) carriers we found dysregulation of microglia, phagocytosis and the phagocytic receptors MERTK and AXL.
Read the full summary ↓
Exogenous progranulin regulated MERTK and AXL RNA expression in human microglia induced from iPSCs irrespective of GRN mutation status, without directly binding to MERTK or AXL proteins. We generated double knock-out mice and found that constitutive homozygous loss of Grn and Mertk (Grn-/-;Mertk-/-) rescued microglial disease signature while constitutive homozygous loss of Grn and Axl (Grn-/-;Axl-/-) worsened the microglial disease signature. Higher levels of AXL protein, but not MERTK protein, in the post-mortem superior temporal gyrus correlated with worse cross-sectional functional impairment (CDR sum of boxes) by both GRN+/- mutation carriers and non-carrier controls. These data explain in part the inflammation seen in GRN-FTD and are applicable to other inflammatory states in which PGRN, MERTK and AXL play regulatory roles, including cancer, sepsis, stroke, diabetes and obesity. The interaction between GRN, MERTK and AXL opens potential new therapeutic avenues to intervene on this inflammatory axis.
Published in
Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD
Clelland CD, Fan L, Saloner R et al. · Communications biology 2025 · PMID 40596721 · doi:10.1038/s42003-025-08368-2
This dataset
Open GSE250280 in finder → Find more 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 GSE250280_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 PRJNA1053290 and SRA study SRP478238. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40596721) ↗
Study design
7 conditions, mostly with about 4 replicates each
Non ×8 LG332 ×8 FTD ×7 LG180 ×4 LG324 ×4 Axl ×4 LG333 ×4

Supports a between-group comparison across 39 samples.

How we read this: 7 replicated groups read from 39 sample titles; they account for 39 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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