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STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation

GSE283768 Mus musculus (mouse) Single-nucleus RNA-seq 30 samples Submitted 2025/04/23 Platform GPL34290Platform GPL21626Platform GPL24247Platform GPL21697
At a glance

Single-nucleus RNA-seq · mouse · 30 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
Mus musculus (mouse)
Samples
30 samples: 13 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
STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disordersMolecular cell · 2025
Summary (written by the submitters)
Lysosomes are essential organelles for cellular homeostasis. Defective lysosomes are associated with many human diseases, such as lysosomal storage disorders (LSD). How the cell detects lysosomal defects and then restores lysosomal function remain incompletely understood. Here, we show that STING mediates a common neuroinflammatory gene signature in three distinct lysosomal storage disorders, Galctwi/twi, Ppt1-/-, and Cln7-/-.
Read the full summary ↓
Transcriptomic analysis of Galctwi/twi brain tissue revealed that STING also mediates the expression of a broad panel of lysosomal genes that are part of the CLEAR (Coordinated Lysosomal Expression and Regulation) signaling pathway, which is regulated by transcriptional factor EB (TFEB). Immunohistochemical and single-nucleus RNA-seq analysis show that STING regulates lysosomal gene expression in microglia in LSD mice. Mechanistically, we show that STING activation in both human and mouse cells leads to TFEB dephosphorylation, nuclear translocation, and expression of target lysosomal genes. In addition, STING-mediated TFEB activation requires its proton channel function, the V-ATPase-ATG5-ATG8 cascade, and is independent of immune signaling. Functionally, we show that the STING-proton channel-TFEB axis plays a role in facilitating lysosomal repair. Together, our data identify STING-TFEB as a lysosomal quality control and recovery mechanism that responds to both genetic and chemically induced lysosomal dysfunction.
Published in
STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disorders
Tang Z, Xing C, Araszkiewicz A et al. · Molecular cell 2025 · PMID 40185098 · doi:10.1016/j.molcel.2025.03.008
This dataset
Open GSE283768 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 GSE283768_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 PRJNA1195557 and SRA study SRP550053. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40185098) ↗
Study design
13 conditions, mostly in duplicate
Galc+/+, 32days, ×3 Galctwi/twi, 32days, ×3 Galctwi/twi Sting-/, 32days, ×2 MEF Vehicle treated 10h, ×2 MEF DMXAA treated 10h, ×2 STING KO MEF Vehicle treated 10h, ×2 STING KO MEF DMXAA treated 10h, ×2 BJ1 Vehicle treated 8h, ×2 +7 more

Supports a between-group comparison across 28 samples.

How we read this: 13 replicated groups read from 30 sample titles; they account for 28 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
Datasets on a similar topic

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