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NOD2 drives regenerative fetal-like reprogramming in the intestinal epithelium

GSE295472 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2026/04/29 Platform GPL21493Platform GPL34328
At a glance

RNA-seq (gene expression) · mouse · 15 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
15 samples: 3 × Ileal organoid, control, vs 3 × Ileal organoid, L18-MDP, vs 3 × Ileal organoid, IFNg+TNF, vs 3 × Ileal organoid, IFNg+TNF+L18-MDP,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
NOD2 drives regenerative fetal-like reprogramming in the intestinal epitheliumProceedings of the National Academy of Sciences of the United States of America · 2026
Summary (written by the submitters)
Inflammatory injury to the intestine triggers a reprogramming of the intestinal epithelium to a fetal-like state, facilitating rapid restoration of the epithelial barrier. Although the intestinal microbiota is a key modulator of inflammation, its role in driving epithelial fetal-like reversion and promoting restitution remains unclear.
Read the full summary ↓
Using irradiation (IR) injury as a model for small intestinal epithelium restitution, we found that the intestinal microbiota accelerated epithelial restitution by amplifying a repair-associated inflammatory response that promoted the emergence of fetal-like intestinal epithelial cells (IECs), marked by Ly6a and Clu. NOD2, the strongest genetic link to the development of Crohn’s disease, was expressed in fetal-like IECs following injury. Notably, stimulation of NOD2 by its peptidoglycan ligand in an ileal organoid model potentiated an inflammatory gene signature characterized by interferon (IFN) signaling, coinciding with enterocyte recovery. NOD2 deficiency exacerbated epithelial apoptosis following IR injury, while epithelial-specific NOD2 signaling promoted the emergence of fetal-like IECs and enhanced epithelial proliferation. Together, these results identify a critical role for microbiota and microbial sensing by NOD2 in controlling the fate of fetal-like IECs following injury, thereby contributing to the protective effect of this microbial sensor during intestinal inflammation.
Published in
NOD2 drives regenerative fetal-like reprogramming in the intestinal epithelium
Tsang DKL, Maisonneuve C, Ayyaz A et al. · Proceedings of the National Academy of Sciences of the United States of America 2026 · PMID 42054366 · doi:10.1073/pnas.2519981123
This dataset
Open GSE295472 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 GSE295472_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 PRJNA1254739 and SRA study SRP580827. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42054366) ↗
Study design
3 × Ileal organoid, control, vs 3 × Ileal organoid, L18-MDP, vs 3 × Ileal organoid, IFNg+TNF, vs 3 × Ileal organoid, IFNg+TNF+L18-MDP,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 15 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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