GEO series

TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients.

GSE291125 Homo sapiens (human) Single-cell RNA-seq 2 samples Submitted 2026/01/20 Platform GPL18573

At a glance

Single-cell RNA-seq · human · 2 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Homo sapiens (human)
Samples: 2 samples: 2 samples, each with a distinct title — no replicated groupsGroups 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: TL1A-activated T cells remodel the rectal mucosa in patients with Crohn's disease with perianal fistulising diseaseGut · 2025

Summary (written by the submitters)

Single-cell RNA sequencing revealed the increased abundance of some cell types, such as intestinal fibroblasts, in the CD-PFD rectal mucosa relative to CD. Within the stromal subset, the lamina propria S1 fibroblasts showed the highest number of differentially expressed genes (DEGs) between CD and CD-PFD patients, including an upregulation of TFPI2 and a downregulation of the TGFβ-responding gene CTGF.

Read the full summary ↓

These changes were validated by bulk RNA analysis, where we also observed overexpression of the previously described PFD target genes MMP1 and MMP3. In vitro studies with intestinal fibroblasts confirmed the negative regulation by TGFβ of the PFD-signature, thus ruling out TGFβ as a driver of the PFD-associated fibroblast signature. Next, we investigated DEGs in the lymphoid compartment and identified lymphotoxin beta (LTB) as being upregulated in CD-PFD intestinal CD4+ T cells. LTB interacts with its receptor LTBR, which is expressed in stromal, epithelial and myeloid cells. Interestingly, LTB-LTBR interactions were increased in the CD-PFD group. In vitro studies in primary fibroblasts showed that LTB upregulates TFPI2, while it downregulates CTGF, thus reproducing the PFD-associated signature. Finally, we submitted the top 50 genes overexpressed by CD-PFD CD4+ T cells to the immune dictionary1, which identified TL1A as its most likely driver. In line with this, the TL1A receptor TNFRSF25 was overexpressed in CD-PFD CD4+ T cells. As a link between TL1A and LTB is not described in the literature, we stimulated anti-CD3-activated peripheral T cells with TL1A and observed the significant upregulation of LTa1b2, the functional form of LTB. Intriguingly, we also observed that while TNF can drive the PFD-associated signature in fibroblasts, it cannot induce LTa1b2 in T cells, suggesting that TNF and TL1A/LTB signalling are two independent but potentially complementary pathways in PFD. In summary, we propose a previously unrecognized TL1A-LTB axis as being responsible for inducing PFD-associated alterations in the rectal mucosa, and we hypothesise that inhibition of TL1A might be worth exploring in the context of perianal disease.

Published in

TL1A-activated T cells remodel the rectal mucosa in patients with Crohn's disease with perianal fistulising disease

Gudiño V, Cho JW, Caballol B et al. · Gut 2025 · PMID 41448881 · doi:10.1136/gutjnl-2025-336246

This dataset

Open GSE291125 in finder → Find more human 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 GSE291125_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 PRJNA1232049 and SRA study SRP568049. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41448881) ↗

Study design

2 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 2 sample titles: 2 distinct titles with little repetition. 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

GSM8829438 PFD-006-T0-N
GSM8829439 PFD-008-T0-N

Datasets on a similar topic

GSE290220 TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients [scRNA-seq] 29 samples shares disease-associated, tl1a-activated, fistulizing, regulators, upstream, perianal, changes, tcells
GSE291014 TL1A-activated Tcells as upstream regulators of perianal fistulizing disease-associated changes in the rectum of Crohn's Disease patients [RNA-seq] 28 samples shares disease-associated, tl1a-activated, fistulizing, regulators, upstream, perianal, changes, tcells
GSE256497 COMPARATIVE SINGLE CELL PROFILING OF MUCOSA AND ORGANOIDS IMPLICATES ALTERED EPITHELIAL-MESENCHYMAL INTERACTIONS MEDIATED BY PTGER4 IN PERIANAL FISTULIZING CROHN’S DISEASE 44 samples shares fistulizing, perianal
GSE293514 Development of a split-toxin CRISPR screening platform to systematically identify upstream regulators of human myoblast fusion 57 samples shares regulators, upstream
GSE277387 Single-Cell and Spatial Multi-omics Reveal Interferon Signaling in the Pathogenesis of Perianal Fistulizing Crohn’s Disease 21 samples shares fistulizing, perianal
GSE52529 Pseudo-temporal ordering of individual cells reveals regulators of differentiation 384 samples shares regulators
GSE300841 Deciphering the functional impact of Alzheimer’s Disease-associated variants in resting and proinflammatory immune cells [crispr] 116 samples shares disease-associated
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