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← IBD spatial transcriptomics

Divergent spatial microdomains drive inflammation and repair in Ulcerative and Immune Checkpoint Therapy Colitis - Spatial Transcriptomics

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Dataset overview

Participants None
Samples 16
Reuse readiness 6.1/10 evidence-backed score

Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis.

Gupta T, Antanaviciute A, Hyun-Jung Lee C, Ottakandathil Babu R, Aulicino A, Christoforidou Z, Siejka-Zielinska P, O'Brien-Ball C, et al. · Cancer cell · 2024

Abstract

The success of checkpoint inhibitors (CPIs) for cancer has been tempered by immune-related adverse effects including colitis. CPI-induced colitis is hallmarked by expansion of resident mucosal IFNγ cytotoxic CD8<sup>+</sup> T cells, but how these arise is unclear. Here, we track CPI-bound T cells in intestinal tissue using multimodal single-cell and subcellular spatial transcriptomics (ST). Target occupancy was increased in inflamed tissue, with drug-bound T cells located in distinct microdomains distinguished by specific intercellular signaling and transcriptional gradients. CPI-bound cells were largely CD4<sup>+</sup> T cells, including enrichment in CPI-bound peripheral helper, follicular helper, and regulatory T cells. IFNγ CD8<sup>+</sup> T cells emerged from both tissue-resident memory (TRM) and peripheral populations, displayed more restricted target occupancy profiles, and co-localized with damaged epithelial microdomains lacking effective regulatory cues. Our multimodal analysis identifies causal pathways and constitutes a resource to inform novel preventive strategies.

doi:10.1016/j.ccell.2024.04.010 ↗ PMID 38744246 ↗ PMC12979251 ↗

Study facts

Organism
Homo sapiens
Platform
10x Visium
Age group
adult
Disease groups
—
Anatomical sites
Colon tissue

Data availability

  • Raw counts
  • Spatial coordinates
  • Histology images

File types ZIP

Strengths & limitations for reuse

Strengths

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

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

FieldValueEvidence
assay.platform 10x Visium
using the 10X visium platform

Section series_overall_design, offset —
assay.platform_version Space Ranger 1.0
Fastq files were processed using 10x Genomics Spaceranger (version 1.0) software

Section sample.data_processing, offset —
assay.reference_genome hg38 from source
hg38

Section GEO family SOFT, offset —
assay.resolution spot inferred
raw feature barcode matrix in mtx format... spot barcodes... spot position to image pixel coordinates

Section sample.data_processing, offset —
assay.sequencing_based True from source
GEO assay type/library strategy: RNA-SEQ

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

Section GEO family SOFT, offset —

Cohort

FieldValueEvidence
cohort.age_group adult from source
GEO age characteristics: 33; 53; 47; 72; 74; 74; 30; 30; 30; 66; 55; 60; 65; 75; 46; 41

Section GEO family SOFT, offset —
cohort.disease_activity_metadata_available True from source
GEO sample characteristics document disease activity

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

Section GEO family SOFT, offset —

Data_Assets

FieldValueEvidence
data_assets.environment_or_container_info True
Fastq files were processed using 10x Genomics Spaceranger (version 1.0) software

Section sample.data_processing, offset —
data_assets.file_manifest True from source
Supplementary files enumerated in family SOFT ()

Section GEO family SOFT, offset —
data_assets.histology_images True
spatial transcriptomics slide H&E image in jpeg format

Section sample.data_processing, offset —
data_assets.open_access True
Public on Apr 12 2024

Section series_status, offset —
data_assets.raw_counts True
Spaceranger outputs - raw feature barcode matrix in mtx format

Section sample.data_processing, offset —
data_assets.spatial_coordinates True
spot position to image pixel coordinates

Section sample.data_processing, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['Colon tissue'] from source
GEO sample source names: Colon 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 16 computed
16 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
specimens.preservation_method freshly frozen in OCT blocks
Adult colonic samples were freshly frozen in OCT blocks

Section sample.extract_protocol, offset —
specimens.specimen_type mixed from source
GEO samples include biopsy and resection

Section GEO family SOFT, offset —