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A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease

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Dataset overview

Participants None
Samples 51
Reuse readiness 5.9/10 evidence-backed score

A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease.

Pang J, Al-Ani AH, Patel KM, Zhou Y, Young SN, Chen J, Kong I, Barrios M, et al. · Science (New York, N.Y.) · 2026

Abstract

Inflammatory bowel disease (IBD) is a chronic condition caused by altered cytokine signaling, maladaptive immunity, dysbiosis, and intestinal barrier dysfunction. Although current therapies aim to correct these imbalances to induce remission, most patients ultimately relapse, suggesting that key pathogenic mechanisms persist. Here, we identified aberrant epithelial cell death signaling as an underlying feature of IBD that arises in patients in remission and on advanced therapy. Mechanistically, nascent inflammation skewed epithelial cells into an M1-macrophage-like transcriptional state that promoted RIPK1-independent necroptotic signaling. This signaling then triggered inducible nitric oxide synthase-assisted mitochondrial apoptosis of absorptive epithelial cells and PUMA-mediated intestinal stem cell death. Thus, aberrant epithelial cell death signaling represents a hallmark of IBD that occurs early in mucosal lesion development, persists despite current therapeutic strategies, and predicts clinical relapse.

doi:10.1126/science.aeh7112 ↗ PMID 42658927 ↗

Study facts

Organism
Homo sapiens
Platform
Xenium
Age group
—
Disease groups
—
Anatomical sites
Ascending colon, Caecum, Sigmoid colon, Rectum, Transverse colon, Terminal ileum, Descending colon

Data availability

  • Raw counts
  • Processed matrix
  • Spatial coordinates
  • Histology images

File types H5PARQUETTIFF

Strengths & limitations for reuse

Strengths

  • Raw counts are advertised
  • Processed matrices are advertised
  • Spatial coordinates are advertised
  • Histology images are advertised

Limitations

  • 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.panel_size 475
profile the expression of 475 genes

Section series_summary, offset —
assay.platform Xenium
mounted directly onto Xenium slides (10x Genomics, Cat#PN-1000460)

Section extract_protocol, offset 1700
assay.platform_version Xenium Ranger v4.0.1.1 from source
Xenium Ranger v4.0.1.1

Section GEO family SOFT, offset —
assay.resolution subcellular
we used subcellular spatial transcriptomics

Section series_summary, offset —
assay.segmentation_method ProSeg v3.0.10
Cells were segmented using ProSeg v3.0.10.

Section sample_data_processing, offset —
assay.sequencing_based False inferred
re-imported into the original Xenium output bundle using xeniumranger import-segmentation

Section data_processing, offset —
assay.whole_transcriptome False
subcellular spatial transcriptomics to profile the expression of 475 genes

Section series_summary, offset —

Cohort

FieldValueEvidence
cohort.disease_activity_metadata_available True
51 intestinal biopsies with high RNA integrity were chosen to encompass different degrees of inflammation, intestinal sites, IBD subtypes and treatment classes.

Section series_overall_design, offset —
cohort.treatment_exposure_documented True from source
GEO sample characteristics document treatment/therapy

Section GEO family SOFT, offset —

Data_Assets

FieldValueEvidence
data_assets.file_manifest True
GSE330953_RAW.tar

Section filelist.txt, offset —
data_assets.histology_images True from source
GEO deposit evidence: TIFF in GEO suppfile types

Section GEO record summary, offset —
data_assets.molecule_coordinates True
including transcript assignments and cell polygons

Section samples.data_processing, offset —
data_assets.open_access True
Public on Sep 03 2026

Section series_status, offset —
data_assets.processed_matrix True from source
GEO deposit evidence: H5 in GEO suppfile types

Section GEO record summary, offset —
data_assets.raw_counts True inferred
including cell_feature_matrix.h5, cells.parquet, cell_boundaries.parquet, and transcripts.parquet.

Section samples.data_processing, offset —
data_assets.sample_metadata True
"tissue": "Ascending colon", "study id": "NM044", "ibd status": "Control"

Section characteristics, offset —
data_assets.segmentation_data True
including transcript assignments and cell polygons

Section sample_data_processing, offset —
data_assets.spatial_coordinates True
including cell_feature_matrix.h5, cells.parquet, cell_boundaries.parquet, and transcripts.parquet.

Section samples.data_processing, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['Ascending colon', 'Caecum', 'Sigmoid colon', 'Rectum', 'Transverse colon', 'Terminal ileum', 'Descending colon'] from source
GEO sample source names: Ascending colon; Caecum; Sigmoid colon; Rectum; Transverse colon; Terminal ileum; Descending colon

Section GEO family SOFT, offset —
specimens.inflamed_status_available True from source
GEO sample characteristics report inflammation status

Section GEO family SOFT, offset —
specimens.number_of_samples 51 computed
51 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
specimens.preservation_method FFPE
tissue preservation method: FFPE

Section sample_characteristics, offset —
specimens.specimen_type biopsy
Here, we used subcellular spatial transcriptomics to profile the expression of 475 genes in intestinal biopsies from patients with or without inflammatory bowel disease (IBD)

Section series_summary, offset —