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Microbiota-derived polyphosphates govern mucosal immunity through multilevel suppression of STAT/IL-27 signaling (multiome)

GSE269703 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 16 samples Submitted 2026/03/17 Platform GPL30172
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 16 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Mus musculus (mouse)
Samples
16 samples: 4 × Unstimulated, snRNA-seq, vs 4 × Unstimulated, snATAC-seq, vs 4 × Long-chain polyphosphate stimulated, snRNA-seq, vs 4 × Long-chain polyphosphate stimulated, snATAC-seq,Groups 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
Proton-activated chloride channel 1 is essential for innate host defense against bacterial sepsisProceedings of the National Academy of Sciences of the United States of America · 2026
Summary (written by the submitters)
The interplay between gut bacteria and mucosal immune cells is crucial for maintaining intestinal homeostasis. Dysregulation of this immune-microbiome axis has been implicated in the pathogenesis of inflammatory bowel diseases, but the mechanisms driving the health-to-disease transition remain unclear. Here, we demonstrate that polyphosphates, a bacterial metabolite, influence mucosal immunity during both homeostasis and inflammation.
Read the full summary ↓
Germ-free mice were monocolonized with polyphosphate competent Escherichia coli or a ∆ppk E. coli mutant strain deficient in polyphosphate production, affecting subsets of T cells and mononuclear phagocytes. Transfer of lamina propria immune cells into RAG1-/- mice indicated that polyphosphate-experienced T cells induced more severe colitis. Mechanistically, polyphosphate exposure suppressed chromatin accessibility of the Stat1, Stat3 and Il10 genes in CD4+ T cells. Ultra-pure polyphosphates corresponding to the molecular sizes produced by microbes decreased gene expression of STATs as observed by snRNA-seq, antagonized IL-27 production in mononuclear phagocytes through suppression of STAT1, and disrupted IL-27-induced STAT1/STAT3 phosphorylation in naïve CD4+ and CD8+ T cells. IL-27Rα-/- lamina propria immune cells were more aggressive in promoting colitis, suggesting that the paralyzing effects of polyphosphates on IL-27/IL-27Rα signaling are functionally significant. In conclusion, the intestinal microbiota utilizes polyphosphates to disrupt the protective balance of innate and adaptive immune cell networks.
Published in
Proton-activated chloride channel 1 is essential for innate host defense against bacterial sepsis
Garo LP, Brueck K, Walachowski S et al. · Proceedings of the National Academy of Sciences of the United States of America 2026 · PMID 41941636 · doi:10.1073/pnas.2515768123
This dataset
Open GSE269703 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 GSE269703_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1123261 and SRA study SRP513602. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41941636) ↗
Study design
4 × Unstimulated, snRNA-seq, vs 4 × Unstimulated, snATAC-seq, vs 4 × Long-chain polyphosphate stimulated, snRNA-seq, vs 4 × Long-chain polyphosphate stimulated, snATAC-seq,

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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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