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MIWI2 Regulates Mitochondrial Gene Expression During Influenza and Exacerbates Disease Outcome

GSE276578 Mus musculus (mouse) Non-coding RNA profiling 64 samples Submitted 2025/02/25 Platform GPL21626Platform GPL24247
At a glance

Non-coding RNA profiling · mouse · 64 samples

What it is
Non-coding RNA profilingLevels of RNAs that do not code for proteins, such as miRNA or lncRNA.
Organism
Mus musculus (mouse)
Samples
64 samples: 16 conditions, mostly with about 4 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
Somatic Miwi2 modulates mitochondrial function in airway multiciliated cells and exacerbates influenza pathogenesisiScience · 2025
Summary (written by the submitters)
The airway epithelium, consisting of diverse cell types, plays a vital role in defending against respiratory viruses. MIWI2 multiciliated (M2MC) cells are a rare subpopulation of multiciliated cells distinguished by the expression of MIWI2, the mouse analogous PIWIL4 argonaute family protein. While recognized for its role in repressing retrotransposons during spermatogenesis and regulating viral RNA in mosquitos, the function of MIWI2 in M2MC cells remains poorly understood.
Read the full summary ↓
This study explores the transcriptomic changes in retrotransposons, viral RNAs, and host genes in an effort to elucidate MIWI2’s role in the airway. M2MC and nonM2MC cells were sorted from digested lungs of MIWI2 haplosufficient (Miwi2+/tom) and deficient (Miwi2tom/tom) mice intratracheally instilled with saline or mouse adapted A/Puerto Rico/8/1934 (PR8) IAV three days post infection. Our findings indicated that retrotransposon and viral RNA expression is independent of MIWI2 expression. However, MIWI2 deficiency decreased mitochondrial and ribosomal gene expression in M2MC cells during PR8 infection. In addition, a decrease in small RNAs mapped to nuclear mitochondrial (NuMT) DNA was observed in saline treated MIWI2 expressing cells. These findings were then followed up by flow cytometry studies where an increase in intracellular reactive oxygen species (ROS) was observed in PR8 infected multiciliated cells from Miwi2tom/tom mice. In addition, Miwi2tom/tom mice experience decreased viral titer and RNA 7 days post infection and recovered faster in percent body weight compared to wild-type and Miwi2+/tom mice. These studies suggest that MIWI2 exacerbates IAV outcomes by regulating mitochondrial gene expression and function. These results reveal a novel role for MIWI2 in somatic cells and propose MIWI2/PIWIL4 as a potential biomarker for susceptibility to severe respiratory infections. Understanding MIWI2-dependent pathways could lead to new therapeutic targets for respiratory viral infections.
Published in
Somatic Miwi2 modulates mitochondrial function in airway multiciliated cells and exacerbates influenza pathogenesis
Vasquez JH, Yuan J, Leow CJ et al. · iScience 2025 · PMID 40241756 · doi:10.1016/j.isci.2025.112291
This dataset
Open GSE276578 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 GSE276578_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 ↗

Also filed as BioProject PRJNA1157873 and SRA study SRP531188. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40241756) ↗
Study design
16 conditions, mostly with about 4 replicates each
small_RNA_PR8_nonM2MC_Haplosufficient ×4 small_RNA_PR8_M2MC_Haplosufficient ×4 small_RNA_PR8_nonM2MC_Deficient ×4 small_RNA_PR8_M2MC_Deficient ×4 small_RNA_Saline_nonM2MC_Haplosufficient ×4 small_RNA_Saline_M2MC_Haplosufficient ×4 small_RNA_Saline_nonM2MC_Deficient ×4 small_RNA_Saline_M2MC_Deficient ×4 +8 more

Supports a between-group comparison across 64 samples.

How we read this: 16 replicated groups read from 64 sample titles; they account for 64 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

+ 24 more — browse all 64 samples with per-sample file links →

Datasets on a similar topic

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