GEO series

Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection

GSE282408 Mus musculus (mouse) RNA-seq (gene expression) 30 samples Submitted 2025/12/04 Platform GPL21103

At a glance

RNA-seq (gene expression) · mouse · 30 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: 30 samples: 6 conditions, mostly with about 6 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: Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infectionNature communications · 2025

Summary (written by the submitters)

Inflammation and cytokine release are hallmarks of severe COVID-19. While pro-grammed cell death is known to drive inflammation, its role in SARS-CoV-2 patho-genesis remains unclear. Using gene-targeted murine COVID-19 models with tran-scriptomic and proteomic analyses, we found that caspase-8 is critical for cytokine release and inflammation.

Read the full summary ↓

Loss of caspase-8 reduced disease severity and viral loads in mice, and interestingly, this occurred independently of its apoptotic func-tion. Instead, reduction in SARS-CoV-2 pathology was linked to decreased IL-1β levels and inflammation. Loss of pyroptosis and necroptosis mediators, in gene-targeted animals, provided no additional benefits in mitigating disease outcomes beyond that conferred by loss of caspase-8. Transcriptional profiling of caspase-8 knockout animals confirmed that improved outcomes were due to reduced pro-inflammatory responses, rather than changes in cell death signaling. Elevated ex-pression of caspase-8 and FLIP in infected lungs, alongside caspase-8 mediated cleavage of the NF-kB signaling suppressor N4BP1, suggests a role of this signal-ing axis in overt inflammation. Collectively, these findings highlight non-apoptotic caspase-8 as a driver of severe COVID-19 through modulation of inflammation, not through the induction of apoptosis.

Published in

Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection

M Bader S, Scherer L, Bhandari R et al. · Nature communications 2025 · PMID 41233351 · doi:10.1038/s41467-025-65098-z

This dataset

Open GSE282408 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 GSE282408_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 PRJNA1188515 and SRA study SRP546387. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41233351) ↗

Study design

6 conditions, mostly with about 6 replicates each

Lung, quad_p21 ×6 Lung, quint_p21 ×6 Lung, wt_p21 ×6 Lung, quad_mock ×4 Lung, quint_mock ×4 Lung, wt_mock ×4

Supports a between-group comparison across 30 samples.

How we read this: 6 replicated groups read from 30 sample titles; they account for 30 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

GSM8642662 Lung, quad_p21_1 Lung, quad_p21
GSM8642663 Lung, quad_p21_5 Lung, quad_p21
GSM8642664 Lung, quad_mock_1 Lung, quad_mock
GSM8642665 Lung, quad_mock_2 Lung, quad_mock
GSM8642666 Lung, quad_mock_3 Lung, quad_mock
GSM8642667 Lung, quad_mock_4 Lung, quad_mock
GSM8642668 Lung, quad_p21_6 Lung, quad_p21
GSM8642669 Lung, quint_p21_5 Lung, quint_p21
GSM8642670 Lung, quint_p21_6 Lung, quint_p21
GSM8642671 Lung, quint_mock_2 Lung, quint_mock
GSM8642672 Lung, quint_mock_3 Lung, quint_mock
GSM8642673 Lung, quad_p21_2 Lung, quad_p21
GSM8642674 Lung, quint_mock_4 Lung, quint_mock
GSM8642675 Lung, wt_p21_1 Lung, wt_p21
GSM8642676 Lung, wt_p21_2 Lung, wt_p21
GSM8642677 Lung, wt_p21_3 Lung, wt_p21
GSM8642678 Lung, wt_p21_4 Lung, wt_p21
GSM8642679 Lung, wt_p21_5 Lung, wt_p21
GSM8642680 Lung, wt_mock_1 Lung, wt_mock
GSM8642681 Lung, wt_mock_2 Lung, wt_mock
GSM8642682 Lung, wt_mock_3 Lung, wt_mock
GSM8642683 Lung, wt_mock_4 Lung, wt_mock
GSM8642684 Lung, quad_p21_3 Lung, quad_p21
GSM8642685 Lung, wt_p21_6 Lung, wt_p21
GSM8642686 Lung, quint_p21_1 Lung, quint_p21
GSM8642687 Lung, quint_p21_2 Lung, quint_p21
GSM8642688 Lung, quint_p21_3 Lung, quint_p21
GSM8642689 Lung, quint_p21_4 Lung, quint_p21
GSM8642690 Lung, quint_mock_1 Lung, quint_mock
GSM8642691 Lung, quad_p21_4 Lung, quad_p21

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