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← IBD spatial transcriptomics

Spatial and single cell transcriptomics reveals cellular crosstalk changes in ileal Crohn’s disease during inflammation

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Dataset overview

Participants 5
Samples 24
Reuse readiness 7.3/10 evidence-backed score

Altered inflammatory mucosal signatures within their spatial and cellular context during active ileal Crohn's disease.

Kolachala VL, Maddipatla SC, Murthy S, Hwang Y, Dodd AF, Sharma G, Munasinghe S, Pelia RS, et al. · JCI insight · 2025

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
Crohn's disease
Anatomical sites
Ileal mucosal cells, Ileal Surgical tissue

Data availability

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

File types CSVJPGJSONMTXPNGTSV

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 counts are documented
Extraction evidence & provenance

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

Assay

FieldValueEvidence
assay.platform 10x Genomics Visium
all processed using the 10x Genomics Visium platform

Section Results / Non-negative matrix factorization demonstrates spatial compartmentalization, offset 19400
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 Methods / ST processing, offset 35200
assay.reference_genome GRCh38 from source
GRCh38

Section GEO family SOFT, offset —
assay.resolution spot
fiducials harboring 5,000 barcoded capturing spots

Section Methods / ST processing, offset 34800
assay.sequencing_based True from source
GEO assay type/library strategy: OTHER, RNA-SEQ

Section GEO family SOFT, offset —
assay.whole_transcriptome True from source
GEO library strategy=['OTHER', 'RNA-SEQ']

Section GEO family SOFT, offset —

Cohort

FieldValueEvidence
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 GEO family SOFT, offset —
cohort.crohns_disease_participants 5
All patients participating in this study were diagnosed with CD... n = 5 patients, 16 sections total.

Section Methods — Patient specimen collection, offset 14900
cohort.disease_activity_metadata_available True
Endoscopic and histological activity scores were evaluated for all 15 patients.

Section Methods / Patient specimen collection, offset 31400
cohort.total_participants 5
Tissue sections obtained from different regions of ileal surgical specimens were processed for ST; n = 5 patients, 16 sections total.

Section Methods — Patient specimen collection, offset 15000

Data_Assets

FieldValueEvidence
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 GEO family SOFT, offset —
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 GEO family SOFT, offset —
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 GEO family SOFT, offset —
data_assets.open_access True
"isOpenAccess": "Y"

Section publication metadata, offset —
data_assets.processed_matrix True
aligned to human reference genome GRCh38 to generate count matrices using 10x Cell Ranger and Space Ranger

Section Sample data_processing, offset 6000
data_assets.raw_counts True from source
GEO deposit evidence: MTX in GEO suppfile types

Section GEO record summary, offset —
data_assets.sample_metadata True
"series_sample_id": "GSM7119390 ... GSM7119413"

Section samples, offset —
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 GEO family SOFT, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['Ileal mucosal cells', 'Ileal Surgical tissue'] from source
GEO sample source names: Ileal mucosal cells; Ileal Surgical tissue

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 24 computed
24 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
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 Methods / Patient specimen collection, offset 31600
specimens.preservation_method Flash-frozen in optimal cutting temperature compound using an ultracold isopentane/liquid nitrogen bath
Surgical resections of CD mucosa ... were flash-frozen in optimal cutting temperature compound using an ultracold isopentane/liquid nitrogen bath

Section Methods — ST processing, offset 19000
specimens.specimen_type resection
ST on 16 surgically resected ileal tissues from 4 inflamed and 1 noninflamed CD patients

Section Results — Non-negative matrix factorization demonstrates spatial compartmentalization and localizes active pathways represented in CD, offset 10400