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Paired transcriptomics reveals similarities between cytokine-stimulated organoids and ulcerative colitis epithelial responses

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Dataset overview

Participants None
Samples None
Reuse readiness 6.3/10 evidence-backed score

Patient-matched transcriptomics of in vivo and in vitro colonic epithelium substantiate organoids as a translational model for ulcerative colitis.

Walaas GAE, Sridhar A, Kuraas LF, Sæterstad S, Schioldborg AY, Van Beelen Granlund A, Sandvik AK, Østvik AE, et al. · Scientific reports · 2026

Abstract

Ulcerative colitis (UC) is characterized by cytokine-driven inflammation and barrier disruption in the colon, making epithelial dysfunction central to disease pathology. Intestinal epithelial organoids (IEOs) preserve donor-specific genetics and architecture, offering a promising model, but their ability to replicate patient-specific epithelial inflammation remains undetermined. To directly compare in vivo epithelial transcriptional states with defined cytokine-induced responses in vitro, we analyzed patient-matched transcriptomics from laser microdissected inflamed and uninflamed colonic epithelium and IEOs derived from uninflamed biopsies of the same UC patients. IEOs were stimulated with UC-relevant cytokines (TNF, IFNγ, IFNλ1, or TNF + IFNγ) or a cytokine cocktail (TNF, IL17, IL1β, IL22, Poly(I:C), IFNγ). Key inflammatory genes were validated by immunoblotting and immunostaining. Cytokine-stimulated IEOs recapitulated key in vivo epithelial inflammation, including interferon signaling, antigen presentation, and unfolded protein response pathways. Among the tested conditions, TNF + IFNγ combination and the cytokine cocktail most closely replicated UC epithelial inflammation, with concordance for over 350 UC-relevant genes and protein-level validation of IRF1, ERAP2, NOS2, DUOX2 confirmed patient-dependent expression between inflamed epithelium and cytokine-stimulated IEOs. Our study shows that cytokine-stimulated IEOs provide a robust, personalized platform for modeling epithelial inflammation, enabling discovery of epithelial-specific disease mechanisms and therapeutic targets.

doi:10.1038/s41598-026-54857-7 ↗ PMID 42289443 ↗ PMC13527059 ↗

Study facts

Organism
Homo sapiens
Platform
NovaSeq 6000
Age group
—
Disease groups
Ulcerative colitis
Anatomical sites
—

Data availability

  • Analysis code

Strengths & limitations for reuse

Strengths

  • Raw reads are advertised
  • Analysis code is available
  • Participant-to-sample mapping is available

Limitations

  • Not documented: feature/otu tables are advertised
  • Not documented: taxonomic tables are advertised
  • Not documented: participant counts are documented
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.paired_end True
Paired-end sequencing was performed on the NovaSeq 6000 instrument

Section RNA isolation and sequencing — Intestinal epithelial organoid material, offset 16980
assay.platform NovaSeq 6000
Sequencing was carried out on a NovaSeq6000 platform

Section RNA isolation and sequencing — Laser microdissected material, offset 14380
assay.read_length 59
using an S2 flowcell for 138 cycles with a 59-10-10–59 bp read configuration

Section RNA isolation and sequencing — Laser microdissected material, offset 14460

Cohort

FieldValueEvidence
cohort.disease_activity_metadata_available True
UC patients with active disease (endoscopic Mayo 2/3)

Section Patient cohort, offset 6740
cohort.ulcerative_colitis_participants 12
the same UC patients (n = 12)

Section Patient cohort, offset 6840

Data_Assets

FieldValueEvidence
data_assets.analysis_code True
original code has been deposited at Zenodo and are publicly available

Section Data availability, offset 39720
data_assets.open_access True
are accessible through GEO Series accession numbers GSE288617, GSE288517, GSE289072

Section Data availability, offset 39620
data_assets.pipeline_or_tool_versions True
FASTQ files were generated with bcl2fastq2 Conversion Software v2.20.0.422... FastQC (v0.11.9)... fastp (v0.20.1)

Section Post sequencing processing, offset 17780
data_assets.raw_reads True
The RNA sequencing datasets generated and analyzed during the current study are available in the NCBI's Gene Expression Omnibus (GEO) repository

Section Data availability, offset 39620
data_assets.sample_metadata True
All supplementary materials, including data files and detailed metadata descriptions and original code has been deposited at Zenodo

Section Data availability, offset 39720

Specimens

FieldValueEvidence
specimens.body_site colon
Uninflamed biopsies for laser microdissection and IEO development were acquired from the ascending colon while inflamed biopsies were acquired from an inflamed colonic segment.

Section Patient cohort, offset 7130
specimens.longitudinal_sampling True
Uninflamed biopsies (4–5 per donor) for IEO development were collected from the same patient cohort at 12 months follow-up

Section Patient cohort, offset 6960
specimens.participant_to_sample_mapping_available True
biopsies were simultaneously acquired from the same UC patients

Section Patient cohort, offset 6840
specimens.sample_type mucosal_biopsy
Inflamed and uninflamed biopsies were simultaneously acquired

Section Patient cohort, offset 6810