Genetic profiles of small intestinal and colonic metaplastic Paneth cells by spatial transcriptomics
Download from source ↗Dataset overview
IL-22 induces Paneth cell metaplasia in the colonic epithelium of ulcerative colitis, promoting wound healing via REG3A.
Abstract
Paneth cell metaplasia (PCM) is a phenomenon in which Paneth cells, typically found in the small intestine, appear in the colonic epithelium of patients with ulcerative colitis (UC). Our study demonstrates that the PCM occurrence correlates with disease duration and active inflammation. Furthermore, we identified IL-22, an inflammation-associated cytokine, as a key regulator that promotes PCM formation in the colonic epithelium through suppression of Notch signaling and induces REG3A expression within metaplastic niches. In vitro, we show that Reg3a directly enhances cell proliferation and promotes wound healing using mouse colonic organoids. In vivo, Reg3a<sup>ΔIEC</sup> mice in both acute and chronic DSS-induced colitis models exhibit delayed wound healing. Additionally, studies conducted with patient-derived human colonic organoids revealed that REG3A administration stimulates cell proliferation and accelerates wound healing. Together, these findings support a protective role of PCM-associated REG3A in the colonic epithelium of patients with UC.
doi:10.1038/s41467-026-71136-1 ↗ PMID 41904124 ↗ PMC13195176 ↗
Study facts
- Organism
- Homo sapiens
- Platform
- 10x Genomics Visium HD
- Age group
- adult
- Disease groups
- Ulcerative colitis
- Anatomical sites
- terminal ileum, colon
Data availability
- Raw counts
- Processed matrix
- Spatial coordinates
- Histology images
- Analysis code
File types
JSONMTXPARQUETPNGTIFFTSVTXT
Files and samples
- filelist.txt ↗
- GSE306374_RAW.tar ↗
- GSM9198042_B21_07755_aligned.json.gz ↗
- GSM9198042_B21_07755_barcodes.tsv.gz ↗
- GSM9198042_B21_07755_CytAssist.tif.gz ↗
- GSM9198042_B21_07755_features.tsv.gz ↗
- GSM9198042_B21_07755_HE.tif.gz ↗
- GSM9198042_B21_07755_matrix.mtx.gz ↗
- GSM9198042_B21_07755_scalefactors_json.txt.gz ↗
- GSM9198042_B21_07755_tissue_hires_image.png.gz ↗
- GSM9198042_B21_07755_tissue_lowres_image.png.gz ↗
- GSM9198042_B21_07755_tissue_positions.parquet.gz ↗
- GSM9198043_B22_07388_aligned.json.gz ↗
- GSM9198043_B22_07388_barcodes.tsv.gz ↗
- GSM9198043_B22_07388_CytAssist.tif.gz ↗
- GSM9198043_B22_07388_features.tsv.gz ↗
- GSM9198043_B22_07388_HE.tif.gz ↗
- GSM9198043_B22_07388_matrix.mtx.gz ↗
- GSM9198043_B22_07388_scalefactors_json.txt.gz ↗
- GSM9198043_B22_07388_tissue_hires_image.png.gz ↗
- GSM9198043_B22_07388_tissue_lowres_image.png.gz ↗
- GSM9198043_B22_07388_tissue_positions.parquet.gz ↗
- index.html ↗
- terminal ileum, colon2
| Accession | Sample | Tissue | Molecule |
|---|---|---|---|
GSM9198042 |
Ulcerative colitis patient 1 - terminal ileum biopsy, and sigmoid colon biopsy [UC01_TI_SCA40] | terminal ileum, colon | total RNA |
GSM9198043 |
Ulcerative colitis patient 2 - terminal ileum biopsy, and rectum biopsy [UC02_TL_RE] | terminal ileum, colon | total RNA |
Strengths & limitations for reuse
Strengths
- Raw counts are advertised
- Processed matrices are advertised
- Spatial coordinates are advertised
- Histology images are advertised
- Analysis code is available
- Participant-to-sample mapping is available
- Participant counts are documented
Extraction evidence & provenance
Each extracted field is shown with the source excerpt and location used to resolve it.
Assay
| Field | Value | Evidence |
|---|---|---|
assay.platform |
10x Genomics Visium HD |
mounted on Visium HD slides (10x Genomics) Section |
assay.platform_version |
Space Ranger v3.0.0 from source |
Space Ranger v3.0.0 Section |
assay.reference_genome |
GRCh38 from source |
GRCh38 Section |
assay.resolution |
cellular |
spatial transcriptomics, with near single-cell resolution Section |
assay.sequencing_based |
True from source |
GEO assay type/library strategy: OTHER Section |
assay.whole_transcriptome |
True inferred |
Released mRNA molecules hybridized to spatially barcoded capture oligonucleotides on the slide surface. Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.age_group |
adult |
Human intestinal biopsy samples and ESD specimens were obtained from adult patients of both sexes Section |
cohort.study_design |
cross_sectional inferred |
biopsies were obtained from two ulcerative colitis patients during endoscopy. Section |
cohort.total_participants |
2 |
Paired terminal ileum and colon biopsies were obtained from two ulcerative colitis patients during endoscopy. Section |
cohort.ulcerative_colitis_participants |
2 |
Paired terminal ileum and colon biopsies were obtained from two ulcerative colitis patients during endoscopy. Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
data_assets.analysis_code |
True from source |
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM9198nnn/GSM9198042/suppl/GSM9198042_B21_07755_barcodes.tsv.gz Section |
data_assets.file_manifest |
True from source |
Supplementary files enumerated in family SOFT (ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM9198nnn/GSM9198042/suppl/GSM9198042_B21_07755_barcodes.tsv.gz, ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM9198nnn/GSM9198042/suppl/GSM9198042_B21_07755_tissue_hires_image.png.gz, ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM9198nnn/GSM9198042/suppl/GSM9198042_B21_07755_tissue_positions.parquet.gz) Section |
data_assets.histology_images |
True from source |
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM9198nnn/GSM9198042/suppl/GSM9198042_B21_07755_tissue_hires_image.png.gz Section |
data_assets.open_access |
True |
Public on Jan 26 2026 Section |
data_assets.processed_matrix |
True |
matrix.mtx.gz : gene expressin count data in Matrix Market Exchange Format Section |
data_assets.raw_counts |
True from source |
GEO deposit evidence: MTX in GEO suppfile types Section |
data_assets.spatial_coordinates |
True from source |
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM9198nnn/GSM9198042/suppl/GSM9198042_B21_07755_tissue_positions.parquet.gz Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.anatomical_sites |
['terminal ileum, colon'] from source |
GEO sample source names: terminal ileum, colon Section |
specimens.number_of_samples |
2 computed |
2 GSM records parsed from GEO family SOFT Section |
specimens.participant_to_sample_mapping_available |
True |
Ulcerative colitis patient 1 Section |
specimens.participant_to_section_mapping_available |
True |
Paired terminal ileum and colon biopsies were obtained from two ulcerative colitis patients Section |
specimens.preservation_method |
formalin-fixed paraffin-embedded (FFPE) |
Formalin-fixed paraffin-embedded (FFPE) tissue sections were cut at a thickness of 5 µm Section |
specimens.specimen_type |
biopsy |
terminal ileum biopsy, and sigmoid colon biopsy Section |