GEO series

Proteasome dysfunction in T cells causes immunodeficiency via cell cycle disruption and apoptosis

GSE291117 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/05/19 Platform GPL28457

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
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: Proteasome dysfunction in T cells causes immunodeficiency via cell cycle disruption and apoptosisInternational immunology · 2025

Summary (written by the submitters)

Proteasomes are essential molecular complex that regulate intracellular protein homeostasis by selectively degrading ubiquitinated proteins. Genetic mutations in subunits of proteasomes leads to proteasome-associated autoinflammatory syndromes (PRAAS) characterized by autoinflammation, partial progressive lipodystrophy, and in certain mutations, immunodeficiency.

Read the full summary ↓

However, the molecular mechanisms by which proteasome dysfunction results in these phenotypes remain unclear. Here, we established a mouse that carries a mutation in β5i (encoded by Psmb8) along with T cell specific β5 (encoded by Psmb5) deficiency (KIKO mice). The KIKO mice showed severe loss of mature T cells in the spleen but not in the thymus, with reduced proteasome activity leading to the accumulation of ubiquitinated proteins. The CD4+ T cells of KIKO mice showed impaired proliferative activity with cell cycle arrest in G0/G1 phase following TCR engagement. T cells of KIKO mice underwent rapid cell death through apoptosis, as treatment of T cells with a caspase inhibitor Z-VAD rescued cell viability. Moreover, proteasome dysfunction induced apoptosis in T cells without either affecting mitochondrial functions or ER stress responses. Thus, our data provide insight into the molecular mechanisms underlying not only for immunodeficiency in PRAAS but also for T cell deficiency associated other disorders.

Published in

Proteasome dysfunction in T cells causes immunodeficiency via cell cycle disruption and apoptosis

Shinebaatar E, Morimoto J, Koga R et al. · International immunology 2025 · PMID 40223594 · doi:10.1093/intimm/dxaf021

This dataset

Open GSE291117 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 GSE291117_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 PRJNA1232018 and SRA study SRP568034. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40223594) ↗

Samples in this study

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+ 12 more — browse all 12 samples with per-sample file links →

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