Spatial and single cell transcriptomics reveals cellular crosstalk changes in ileal Crohn’s disease during inflammation
Download from source ↗Dataset overview
Altered inflammatory mucosal signatures within their spatial and cellular context during active ileal Crohn's disease.
Abstract
Crohn's disease (CD) involves a complex intestinal microenvironment driven by chronic inflammation. While single-cell RNA sequencing has provided valuable insights into this biology, the spatial context is lost during single-cell preparation of mucosal biopsies. To deepen our understanding of the distinct inflammatory signatures of CD and overcome the limitations of single-cell RNA sequencing, we combined spatial transcriptomics of frozen CD surgical tissue sections with single-cell transcriptomics of ileal CD mucosa. Coexpressed genes and cell-cell communication from single-cell analyses and factorized genes from spatial transcriptomics revealed overlapping pathways affected in inflamed CD, like antigen presentation, phagosome activity, cell adhesion, and extracellular matrix. Within the pathways, early epithelial cells showed evidence of significant changes in gene expression and subtype composition, while spatial mapping revealed the location of the events, particularly antigen presentation from epithelial cells in the base of the crypt. Furthermore, we identified early epithelial cells as a potential mediator of the MHC class II pathway during inflammation, which we validated by spatial transcriptomics cell subtype deconvolution. Therefore, the inflammation from CD appears to change the types of interactions detectable between epithelial cells with immune and mesenchymal cells, likely promoting the conditions for more macrophage infiltration into these inflammatory microdomains.
doi:10.1172/jci.insight.171783 ↗ PMID 40059828 ↗ PMC11949056 ↗
Study facts
- Organism
- Homo sapiens
- Platform
- 10x Genomics Visium
- Age group
- mixed
- Disease groups
- —
- Anatomical sites
- Ileal mucosal cells, Ileal Surgical tissue
Data availability
- Raw counts
- Spatial coordinates
- Histology images
- Analysis code
File types
CSVJPGJSONMTXPNGTSV
Files and samples
- filelist.txt ↗
- GSE228360_RAW.tar ↗
- GSM7119390_Sc1_barcodes.tsv.gz ↗
- GSM7119390_Sc1_features.tsv.gz ↗
- GSM7119390_Sc1_matrix.mtx.gz ↗
- GSM7119391_Sc2_barcodes.tsv.gz ↗
- GSM7119391_Sc2_features.tsv.gz ↗
- GSM7119391_Sc2_matrix.mtx.gz ↗
- GSM7119392_Sc3_barcodes.tsv.gz ↗
- GSM7119392_Sc3_features.tsv.gz ↗
- GSM7119392_Sc3_matrix.mtx.gz ↗
- GSM7119393_Sc4_barcodes.tsv.gz ↗
- GSM7119393_Sc4_features.tsv.gz ↗
- GSM7119393_Sc4_matrix.mtx.gz ↗
- GSM7119394_Sc5_barcodes.tsv.gz ↗
- GSM7119394_Sc5_features.tsv.gz ↗
- GSM7119394_Sc5_matrix.mtx.gz ↗
- GSM7119395_Sc6_barcodes.tsv.gz ↗
- GSM7119395_Sc6_features.tsv.gz ↗
- GSM7119395_Sc6_matrix.mtx.gz ↗
- GSM7119396_Sc7_barcodes.tsv.gz ↗
- GSM7119396_Sc7_features.tsv.gz ↗
- GSM7119396_Sc7_matrix.mtx.gz ↗
- GSM7119397_Sc8_barcodes.tsv.gz ↗
- GSM7119397_Sc8_features.tsv.gz ↗
- GSM7119397_Sc8_matrix.mtx.gz ↗
- GSM7119398_Sc9_barcodes.tsv.gz ↗
- GSM7119398_Sc9_features.tsv.gz ↗
- GSM7119398_Sc9_matrix.mtx.gz ↗
- GSM7119399_Sc10_barcodes.tsv.gz ↗
- GSM7119399_Sc10_features.tsv.gz ↗
- GSM7119399_Sc10_matrix.mtx.gz ↗
- GSM7119400_Sc11_barcodes.tsv.gz ↗
- GSM7119400_Sc11_features.tsv.gz ↗
- GSM7119400_Sc11_matrix.mtx.gz ↗
- GSM7119401_Sc12_barcodes.tsv.gz ↗
- GSM7119401_Sc12_features.tsv.gz ↗
- GSM7119401_Sc12_matrix.mtx.gz ↗
- GSM7119402_ST1_aligned_fiducials.jpg.gz ↗
- GSM7119402_ST1_barcodes.tsv.gz ↗
- GSM7119402_ST1_detected_tissue_image.jpg.gz ↗
- GSM7119402_ST1_features.tsv.gz ↗
- GSM7119402_ST1_matrix.mtx.gz ↗
- GSM7119402_ST1_scalefactors_json.json.gz ↗
- GSM7119402_ST1_tissue_hires_image.png.gz ↗
- GSM7119402_ST1_tissue_lowres_image.png.gz ↗
- GSM7119402_ST1_tissue_positions_list.csv.gz ↗
- GSM7119403_ST2_aligned_fiducials.jpg.gz ↗
- GSM7119403_ST2_barcodes.tsv.gz ↗
- GSM7119403_ST2_detected_tissue_image.jpg.gz ↗
- GSM7119403_ST2_features.tsv.gz ↗
- GSM7119403_ST2_matrix.mtx.gz ↗
- GSM7119403_ST2_scalefactors_json.json.gz ↗
- GSM7119403_ST2_tissue_hires_image.png.gz ↗
- GSM7119403_ST2_tissue_lowres_image.png.gz ↗
- GSM7119403_ST2_tissue_positions_list.csv.gz ↗
- GSM7119404_ST3_aligned_fiducials.jpg.gz ↗
- GSM7119404_ST3_barcodes.tsv.gz ↗
- GSM7119404_ST3_detected_tissue_image.jpg.gz ↗
- GSM7119404_ST3_features.tsv.gz ↗
- GSM7119404_ST3_matrix.mtx.gz ↗
- GSM7119404_ST3_scalefactors_json.json.gz ↗
- GSM7119404_ST3_tissue_hires_image.png.gz ↗
- GSM7119404_ST3_tissue_lowres_image.png.gz ↗
- GSM7119404_ST3_tissue_positions_list.csv.gz ↗
- GSM7119405_ST4_aligned_fiducials.jpg.gz ↗
- GSM7119405_ST4_barcodes.tsv.gz ↗
- GSM7119405_ST4_detected_tissue_image.jpg.gz ↗
- GSM7119405_ST4_features.tsv.gz ↗
- GSM7119405_ST4_matrix.mtx.gz ↗
- GSM7119405_ST4_scalefactors_json.json.gz ↗
- GSM7119405_ST4_tissue_hires_image.png.gz ↗
- GSM7119405_ST4_tissue_lowres_image.png.gz ↗
- GSM7119405_ST4_tissue_positions_list.csv.gz ↗
- GSM7119406_ST5_aligned_fiducials.jpg.gz ↗
- GSM7119406_ST5_barcodes.tsv.gz ↗
- GSM7119406_ST5_detected_tissue_image.jpg.gz ↗
- GSM7119406_ST5_features.tsv.gz ↗
- GSM7119406_ST5_matrix.mtx.gz ↗
- GSM7119406_ST5_scalefactors_json.json.gz ↗
- GSM7119406_ST5_tissue_hires_image.png.gz ↗
- GSM7119406_ST5_tissue_lowres_image.png.gz ↗
- GSM7119406_ST5_tissue_positions_list.csv.gz ↗
- GSM7119407_ST6_aligned_fiducials.jpg.gz ↗
- GSM7119407_ST6_barcodes.tsv.gz ↗
- GSM7119407_ST6_detected_tissue_image.jpg.gz ↗
- GSM7119407_ST6_features.tsv.gz ↗
- GSM7119407_ST6_matrix.mtx.gz ↗
- GSM7119407_ST6_scalefactors_json.json.gz ↗
- GSM7119407_ST6_tissue_hires_image.png.gz ↗
- GSM7119407_ST6_tissue_lowres_image.png.gz ↗
- GSM7119407_ST6_tissue_positions_list.csv.gz ↗
- GSM7119408_ST7_aligned_fiducials.jpg.gz ↗
- GSM7119408_ST7_barcodes.tsv.gz ↗
- GSM7119408_ST7_detected_tissue_image.jpg.gz ↗
- GSM7119408_ST7_features.tsv.gz ↗
- GSM7119408_ST7_matrix.mtx.gz ↗
- GSM7119408_ST7_scalefactors_json.json.gz ↗
- GSM7119408_ST7_tissue_hires_image.png.gz ↗
- GSM7119408_ST7_tissue_lowres_image.png.gz ↗
- GSM7119408_ST7_tissue_positions_list.csv.gz ↗
- GSM7119409_ST8_aligned_fiducials.jpg.gz ↗
- GSM7119409_ST8_barcodes.tsv.gz ↗
- GSM7119409_ST8_detected_tissue_image.jpg.gz ↗
- GSM7119409_ST8_features.tsv.gz ↗
- GSM7119409_ST8_matrix.mtx.gz ↗
- GSM7119409_ST8_scalefactors_json.json.gz ↗
- GSM7119409_ST8_tissue_hires_image.png.gz ↗
- GSM7119409_ST8_tissue_lowres_image.png.gz ↗
- GSM7119409_ST8_tissue_positions_list.csv.gz ↗
- GSM7119410_ST9_aligned_fiducials.jpg.gz ↗
- GSM7119410_ST9_barcodes.tsv.gz ↗
- GSM7119410_ST9_detected_tissue_image.jpg.gz ↗
- GSM7119410_ST9_features.tsv.gz ↗
- GSM7119410_ST9_matrix.mtx.gz ↗
- GSM7119410_ST9_scalefactors_json.json.gz ↗
- GSM7119410_ST9_tissue_hires_image.png.gz ↗
- GSM7119410_ST9_tissue_lowres_image.png.gz ↗
- GSM7119410_ST9_tissue_positions_list.csv.gz ↗
- GSM7119411_ST10_aligned_fiducials.jpg.gz ↗
- GSM7119411_ST10_barcodes.tsv.gz ↗
- GSM7119411_ST10_detected_tissue_image.jpg.gz ↗
- GSM7119411_ST10_features.tsv.gz ↗
- GSM7119411_ST10_matrix.mtx.gz ↗
- GSM7119411_ST10_scalefactors_json.json.gz ↗
- GSM7119411_ST10_tissue_hires_image.png.gz ↗
- GSM7119411_ST10_tissue_lowres_image.png.gz ↗
- GSM7119411_ST10_tissue_positions_list.csv.gz ↗
- GSM7119412_ST11_aligned_fiducials.jpg.gz ↗
- GSM7119412_ST11_barcodes.tsv.gz ↗
- GSM7119412_ST11_detected_tissue_image.jpg.gz ↗
- GSM7119412_ST11_features.tsv.gz ↗
- GSM7119412_ST11_matrix.mtx.gz ↗
- GSM7119412_ST11_scalefactors_json.json.gz ↗
- GSM7119412_ST11_tissue_hires_image.png.gz ↗
- GSM7119412_ST11_tissue_lowres_image.png.gz ↗
- GSM7119412_ST11_tissue_positions_list.csv.gz ↗
- GSM7119413_ST12_aligned_fiducials.jpg.gz ↗
- GSM7119413_ST12_barcodes.tsv.gz ↗
- GSM7119413_ST12_detected_tissue_image.jpg.gz ↗
- GSM7119413_ST12_features.tsv.gz ↗
- GSM7119413_ST12_matrix.mtx.gz ↗
- GSM7119413_ST12_scalefactors_json.json.gz ↗
- GSM7119413_ST12_tissue_hires_image.png.gz ↗
- GSM7119413_ST12_tissue_lowres_image.png.gz ↗
- GSM7119413_ST12_tissue_positions_list.csv.gz ↗
- index.html ↗
- Ileal Surgical tissue12
- Ileal mucosal cells12
| Accession | Sample | Tissue | Molecule |
|---|---|---|---|
GSM7119390 |
Ileal mucosal cells, Crohns Disease [Sc1] | Ileal mucosal cells | polyA RNA |
GSM7119391 |
Ileal mucosal cells, Crohns Disease [Sc2] | Ileal mucosal cells | polyA RNA |
GSM7119392 |
Ileal mucosal cells, Crohns Disease [Sc3] | Ileal mucosal cells | polyA RNA |
GSM7119393 |
Ileal mucosal cells, Crohns Disease [Sc4] | Ileal mucosal cells | polyA RNA |
GSM7119394 |
Ileal mucosal cells, Crohns Disease [Sc5] | Ileal mucosal cells | polyA RNA |
GSM7119395 |
Ileal mucosal cells, Crohns Disease [Sc6] | Ileal mucosal cells | polyA RNA |
GSM7119396 |
Ileal mucosal cells, Crohns Disease [Sc7] | Ileal mucosal cells | polyA RNA |
GSM7119397 |
Ileal mucosal cells, Crohns Disease [Sc8] | Ileal mucosal cells | polyA RNA |
GSM7119398 |
Ileal mucosal cells, Crohns Disease [Sc9] | Ileal mucosal cells | polyA RNA |
GSM7119399 |
Ileal mucosal cells, Crohns Disease [Sc10] | Ileal mucosal cells | polyA RNA |
GSM7119400 |
Ileal mucosal cells, Crohns Disease [Sc11] | Ileal mucosal cells | polyA RNA |
GSM7119401 |
Ileal mucosal cells, Crohns Disease [Sc12] | Ileal mucosal cells | polyA RNA |
GSM7119402 |
Ileal Surgical tissue, Crohns Disease [ST1] | Ileal Surgical tissue | polyA RNA |
GSM7119403 |
Ileal Surgical tissue, Crohns Disease [ST2] | Ileal Surgical tissue | polyA RNA |
GSM7119404 |
Ileal Surgical tissue, Crohns Disease [ST3] | Ileal Surgical tissue | polyA RNA |
GSM7119405 |
Ileal Surgical tissue, Crohns Disease [ST4] | Ileal Surgical tissue | polyA RNA |
GSM7119406 |
Ileal Surgical tissue, Crohns Disease [ST5] | Ileal Surgical tissue | polyA RNA |
GSM7119407 |
Ileal Surgical tissue, Crohns Disease [ST6] | Ileal Surgical tissue | polyA RNA |
GSM7119408 |
Ileal Surgical tissue, Crohns Disease [ST7] | Ileal Surgical tissue | polyA RNA |
GSM7119409 |
Ileal Surgical tissue, Crohns Disease [ST8] | Ileal Surgical tissue | polyA RNA |
GSM7119410 |
Ileal Surgical tissue, Crohns Disease [ST9] | Ileal Surgical tissue | polyA RNA |
GSM7119411 |
Ileal Surgical tissue, Crohns Disease [ST10] | Ileal Surgical tissue | polyA RNA |
GSM7119412 |
Ileal Surgical tissue, Crohns Disease [ST11] | Ileal Surgical tissue | polyA RNA |
GSM7119413 |
Ileal Surgical tissue, Crohns Disease [ST12] | Ileal Surgical tissue | polyA RNA |
Strengths & limitations for reuse
Strengths
- Raw counts are advertised
- Spatial coordinates are advertised
- Histology images are advertised
- Analysis code is available
Limitations
- Not documented: processed matrices 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
| Field | Value | Evidence |
|---|---|---|
assay.platform |
10x Genomics Visium |
all processed using the 10x Genomics Visium platform Section |
assay.platform_version |
Visium Gene Expression Kit; Space Ranger v1.0 |
all using the Visium Gene Expression Kit ... The software 10x Genomics Space Ranger v1.0 was used to align and count Section |
assay.reference_genome |
GRCh38 from source |
GRCh38 Section |
assay.resolution |
spot |
fiducials harboring 5,000 barcoded capturing spots Section |
assay.sequencing_based |
True from source |
GEO assay type/library strategy: OTHER, RNA-SEQ Section |
assay.whole_transcriptome |
True from source |
GEO library strategy=['OTHER', 'RNA-SEQ'] Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.age_group |
mixed from source |
GEO age characteristics: 10; 15; 15; 18; 12; 12; 7; 13; 16; 4; 14; 16; 16; 16; 16; 16; 13; 13; 13; 9; 9; 14; 14; 14 Section |
cohort.disease_activity_metadata_available |
True |
Endoscopic and histological activity scores were evaluated for all 15 patients. Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
data_assets.analysis_code |
True from source |
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM7119nnn/GSM7119390/suppl/GSM7119390_Sc1_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/GSM7119nnn/GSM7119390/suppl/GSM7119390_Sc1_barcodes.tsv.gz, ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM7119nnn/GSM7119402/suppl/GSM7119402_ST1_tissue_hires_image.png.gz, ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM7119nnn/GSM7119402/suppl/GSM7119402_ST1_tissue_positions_list.csv.gz) Section |
data_assets.histology_images |
True from source |
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM7119nnn/GSM7119402/suppl/GSM7119402_ST1_tissue_hires_image.png.gz Section |
data_assets.open_access |
True |
"isOpenAccess": "Y" Section |
data_assets.raw_counts |
True from source |
GEO deposit evidence: MTX in GEO suppfile types Section |
data_assets.sample_metadata |
True |
"series_sample_id": "GSM7119390 ... GSM7119413" Section |
data_assets.spatial_coordinates |
True from source |
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM7119nnn/GSM7119402/suppl/GSM7119402_ST1_tissue_positions_list.csv.gz Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.anatomical_sites |
['Ileal mucosal cells', 'Ileal Surgical tissue'] from source |
GEO sample source names: Ileal mucosal cells; Ileal Surgical tissue Section |
specimens.inflamed_status_available |
True from source |
GEO sample characteristics report inflammation status Section |
specimens.number_of_samples |
24 computed |
24 GSM records parsed from GEO family SOFT Section |
specimens.number_of_tissue_sections |
16 |
Tissue sections obtained from different regions of ileal surgical specimens were processed for ST ... n = 5 patients, 16 sections total. Section |
specimens.preservation_method |
Flash-frozen in optimal cutting temperature compound for spatial tissue sections; biopsies processed immediately after endoscopy |
Surgical resections ... were flash-frozen in optimal cutting temperature compound ... Biopsies were processed immediately after endoscopy Section |
specimens.specimen_type |
mixed |
Ileal tissue and mucosal biopsies from patients with CD undergoing surgery or clinically indicated colonoscopy ... were used in this study. Section |