GEO series

ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits [Microdissected_Motor Neurons]

GSE254228 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/07/09 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 12 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: 12 samples: 6 × 20m_KO vs 6 × 20m_WTGroups 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: ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in miceNature communications · 2025

Summary (written by the submitters)

TANK-Binding Kinase 1 (TBK1) is involved in autophagy and immune signaling. Dominant loss-of-function mutations in TBK1 are linked to Amyotrophic Lateral Sclerosis (ALS), Fronto-temporal dementia (FTD) and ALS/FTD. However, pathogenic mechanisms remain unclear, particularly the cell-type specific disease contributions of TBK1 mutations.

Read the full summary ↓

Here, we focus on cell-specific Tbk1 deletion in motor neurons or microglia. We find that deleting Tbk1 from mouse motor neurons does not induce transcriptional stress, despite lifelong signs of autophagy deregulations. Conversely, Tbk1 deletion in microglia alters their homeostasis and reactive responses. In both spinal cord and brain, Tbk1 deletion leads to a pro-inflammatory, primed microglial signature with features of ageing and neurodegeneration. While it does not induce or modify ALS-like motor neuron damage, microglial Tbk1 deletion causes early FTD-like social recognition deficits. This phenotype is linked to focal microglial activation and T cell infiltration in the substantia nigra pars reticulata and pallidum. Our results reveal that part of TBK1-linked FTD disease originates from microglial dysfunction.

Published in

ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice

Lenoel I, Ribon M, Lorenc F et al. · Nature communications 2025 · PMID 40858618 · doi:10.1038/s41467-025-63211-w

This dataset

Open GSE254228 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 GSE254228_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 PRJNA1069041 and SRA study SRP486029. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40858618) ↗

Study design

6 × 20m_KO vs 6 × 20m_WT

Supports a between-group comparison across 12 samples.

How we read this: 2 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

GSM8036306 20m_KO_1 20m_KO
GSM8036307 20m_KO_2 20m_KO
GSM8036308 20m_KO_3 20m_KO
GSM8036309 20m_KO_4 20m_KO
GSM8036310 20m_KO_5 20m_KO
GSM8036311 20m_KO_6 20m_KO
GSM8036312 20m_WT_1 20m_WT
GSM8036313 20m_WT_2 20m_WT
GSM8036314 20m_WT_3 20m_WT
GSM8036315 20m_WT_4 20m_WT
GSM8036316 20m_WT_5 20m_WT
GSM8036317 20m_WT_6 20m_WT

Datasets on a similar topic

GSE254229 ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice 141 samples shares tbk1, als, recognition, ftd-linked, deficiency, microglial, microglia
GSE254217 ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits. [in vitro_Microglia] 59 samples shares tbk1, als, recognition, ftd-linked, deficiency, microglial, microglia
GSE290810 ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits [FACS_SpinalCord_Microglia & LPS_Brain_SpinalCord] 35 samples shares tbk1, als, recognition, ftd-linked, deficiency, microglial, microglia
GSE306031 Single-Nucleus Transcriptomics Reveals Cell Type-Specific Remodeling and Epilepsy Associated Microglia 31 samples shares als, microglia
GSE327960 Transcription profiles of mouse microglia isolated by FACS from WT and Grn KO animals, separated by lipofuscin levels [hex001110] 24 samples shares als, microglia
GSE288504 Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease [RNA-seq] 15 samples shares als, microglia
GSE341988 Sequential pathogen exposure normalizes the brain neuroimmune microenvironment and reveals a tissue-resident memory CD8 T cell-microglia axis shaping adult neurogenesis 8 samples shares als, microglia
GSE166225 Inference of emergent spatio-temporal processes from single-cell sequencing reveals feedback between de novo DNA methylation and chromatin condensates [RNA-seq] 288 samples shares als

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.