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A neuroepithelial rheostat controls enteric type 1 and type 2 immunity [scRNA-seq]

GSE308755 Mus musculus (mouse) Single-cell RNA-seq 12 samples Submitted 2025/09/29 Platform GPL34328
At a glance

Single-cell RNA-seq · mouse · 12 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Mus musculus (mouse)
Samples
12 samples: 6 conditions, mostly in duplicateGroups 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
Neuroepithelial VIP-VIPR1 interactions differentially control enteric type 1 and type 2 immunityNature immunology · 2025
Summary (written by the submitters)
The nervous and immune systems cooperate to regulate mucosal barrier integrity and host defence. Nevertheless, whether enteric neurons establish neuroepithelial interactions to coordinate immunity remains elusive. Here, we identified a neuroepithelial rheostat that differentially controls type 1 and type 2 immunity. Gut epithelial cells displayed type 1 and type 2 alarmins in distinct circadian cycles, and co-expressed vasoactive intestinal peptide (VIP) receptor 1 (VIPR1), a molecule that integrates diurnal neural-derived VIP signals.
Read the full summary ↓
Chemogenetic modulation of enteric VIPergic neurons led to altered epithelial-derived cytokines and tuft cells. Epithelial-intrinsic deletion of Vipr1 resulted in diminished type 1 immunity signatures, including reduced type 1 alarmins and intra-epithelial lymphocytes (IEL). In contrast, Vipr1 deficiency in epithelial cells led to increased intestinal type 2 immunity, comprising type 2 alarmins, tuft cells and activated group 2 innate lymphoid cells (ILC2). Disruption of these neuroepithelial interactions led to increased susceptibility to bacterial infection, which greatly contrasted with an increased resistance to parasite infection. Our work identifies a neuroepithelial hub that distinctively controls enteric type 1 and type 2 immunity, deciphering a multi-tissue hub that integrates diurnal physiological cues to balance gut immunity and host defence.
Published in
Neuroepithelial VIP-VIPR1 interactions differentially control enteric type 1 and type 2 immunity
Pirzgalska RM, Henriques-Alves B, Raposo B et al. · Nature immunology 2025 · PMID 41286456 · doi:10.1038/s41590-025-02326-0
This dataset
Open GSE308755 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 GSE308755_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1332658 and SRA study SRP624809. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41286456) ↗
Study design
6 conditions, mostly in duplicate
Intestinal epithelial cells from the duodenum… ×2 Intestinal epithelial cells from the ileum C5… ×2 Intestinal epithelial cells from the duodenum… ×2 Intestinal epithelial cells from the ileum Vi… ×2 Intestinal epithelial cells from the duodenum… ×2 Intestinal epithelial cells from the ileum Vi… ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 12 sample titles; they account for 12 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
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