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Rheb modulates mTORC1-independent metabolism is essential for lysosomal function in microglia

GSE279995 Mus musculus (mouse) RNA-seq (gene expression) 14 samples Submitted 2026/06/01 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 14 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
14 samples: 4 × LPS.RHEB.KO vs 4 × LPS.RHEB.WT vs 3 × Ctrl.RHEB.WT vs 3 × Ctrl.RHEB.KOGroups 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.
Summary (written by the submitters)
Microglia are highly motile cells that respond to neuroinflammation and play a crucial role in maintaining CNS homeostasis through their degradation capacity. While metabolic flexibility is vital for peripheral immune cells to sustain cellular function, the adaptation of microglial metabolism to support degradation remains unexplored.
Read the full summary ↓
In this study, we elucidate key metabolic regulatory mechanisms influencing the transcriptional activity in microglia. The loss of Rheb, an activator of mTOR, leads to reduced histone H3 acetylation, resulting in decreased transcription of lysosome-related genes and diminished degradation capacity. Conversely, inhibition of mTORC1 by Mios/GATOR2 or Torin1 enhances microglial lysosomal function, indicating that Rheb regulates lysosome biogenesis independently of mTORC1. Our transcriptional and metabolic profiling reveals that Rheb deficiency prompts microglia to increase glycolysis and glutaminolysis to compensate for a disrupted TCA cycle under environmental challenges. This impaired TCA cycle, correlated with epigenetic modifications, reduces microglia’s ability to clear myelin debris. In contrast, overexpression of Rheb in microglia enhances fAβ clearance in vivo. Our findings demonstrate that metabolic regulation of lysosomal function in microglia is critical for degradation, and enhancing this process offers therapeutic potential for treating age-related neuroinflammatory conditions.
This dataset
Open GSE279995 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 GSE279995_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 PRJNA1175707 and SRA study SRP539991. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
4 × LPS.RHEB.KO vs 4 × LPS.RHEB.WT vs 3 × Ctrl.RHEB.WT vs 3 × Ctrl.RHEB.KO

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 14 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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