Foundry120 atlas

← IBD single-cell transcriptomics

Extended - T and NK cells

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Dataset overview

Participants None
Samples None
Reuse readiness 6.3/10 evidence-backed score

Single-cell integration reveals metaplasia in inflammatory gut diseases.

Oliver AJ, Huang N, Bartolome-Casado R, Li R, Koplev S, Nilsen HR, Moy M, Cakir B, et al. · Nature · 2024

Abstract

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases<sup>1,2</sup> has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease<sup>3</sup>. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn's disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner's glands. Although previously linked to mucosal healing<sup>4</sup>, we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases.

doi:10.1038/s41586-024-07571-1 ↗ PMID 39567783 ↗ PMC11578898 ↗

Study facts

Organism
Homo sapiens
Platform
10x 3' v1
Age group
mixed
Disease groups
—
Anatomical sites
ascending colon, body of stomach, buccal mucosa, caecum, colon, colonic epithelium, colonic mucosa, descending colon, duodenal epithelium, duodenum, epithelium of esophagus, epithelium of rectum, epithelium of small intestine, epithelium of stomach, esophagus, gingiva, ileal epithelium, ileum, ileum lamina propria, intestine, jejunum, labial gland, lamina propria of mucosa of colon, lamina propria of small intestine, mesenteric lymph node, parotid gland, periodontium, pyloric antrum, pylorus, rectosigmoid junction, rectum, sigmoid colon, small intestine, stomach, transverse colon, vermiform appendix

Data availability

  • Processed matrix
  • Analysis code

File types H5AD

Strengths & limitations for reuse

Strengths

  • Processed matrices are advertised
  • Cell metadata are advertised
  • Analysis code is available

Limitations

  • Not documented: raw counts 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.assay_type 10x 3' v1 from source
assay=10x 3' v1

Section structured repository metadata, offset —
assay.sequencing_type scrna_seq from source
sequencing_type=scrna_seq

Section structured repository metadata, offset —

Cohort

FieldValueEvidence
cohort.age_group mixed computed
adult stage; pediatric stage; 10th week post-fertilization stage

Section dataset.development_stage, offset —

Data_Assets

FieldValueEvidence
data_assets.analysis_code True
Additional code including atlas assembly, annotation and downstream analyses is described in detail throughout the Methods; and is available on GitHub ( https://github.com/Teichlab/PanGIAtlas ).

Section Code availability, offset —
data_assets.cell_metadata True from source
CELLxGENE dataset exposes cell metadata

Section structured repository metadata, offset —
data_assets.environment_or_container_info True
All the analyses and plots have been made on standard Python (v3.8 or higher) and R (v4.0.4) environments

Section Code availability, offset —
data_assets.open_access True from source
public CELLxGENE dataset

Section structured repository metadata, offset —
data_assets.processed_matrix True from source
CELLxGENE dataset exposes H5AD

Section structured repository metadata, offset —

Processing

FieldValueEvidence
processing.ambient_rna_correction_reported True
Cellbender v0.2.0 with default parameters was used to remove ambient RNA (soup).

Section Data curation and mapping, offset —
processing.batch_correction_reported True
Cells from healthy/control samples were integrated using scVI

Section Assembly of the healthy reference, offset —
processing.cell_type_annotation_method scANVI/weighted k-nearest-neighbour label transfer with marker-gene review
we performed majority voting of the higher certainty cells (above the cut-off) and marker genes

Section Data projection and label prediction for diseased data, offset —
processing.doublet_detection_reported True
predicted as doublets (based on scrublet score calculated on a per sample basis) are removed

Section scAutoQC, offset —
processing.normalization_method log1p normalization
We used the default processing and normalization of cNMF

Section cNMF analysis, offset —
processing.quality_control_reported True
To uniformly process the data, we remapped raw sequencing data and processed gene counts through our newly developed quality control pipeline (scAutoQC)

Section Pan-gastrointestinal data integration, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['ascending colon', 'body of stomach', 'buccal mucosa', 'caecum', 'colon', 'colonic epithelium', 'colonic mucosa', 'descending colon', 'duodenal epithelium', 'duodenum', 'epithelium of esophagus', 'epithelium of rectum', 'epithelium of small intestine', 'epithelium of stomach', 'esophagus', 'gingiva', 'ileal epithelium', 'ileum', 'ileum lamina propria', 'intestine', 'jejunum', 'labial gland', 'lamina propria of mucosa of colon', 'lamina propria of small intestine', 'mesenteric lymph node', 'parotid gland', 'periodontium', 'pyloric antrum', 'pylorus', 'rectosigmoid junction', 'rectum', 'sigmoid colon', 'small intestine', 'stomach', 'transverse colon', 'vermiform appendix'] from source
tissues=ascending colon, body of stomach, buccal mucosa, caecum, colon, colonic epithelium, colonic mucosa, descending colon, duodenal epithelium, duodenum, epithelium of esophagus, epithelium of rectum, epithelium of small intestine, epithelium of stomach, esophagus, gingiva, ileal epithelium, ileum, ileum lamina propria, intestine, jejunum, labial gland, lamina propria of mucosa of colon, lamina

Section structured repository metadata, offset —
specimens.number_of_cells 262642 from source
cell_count=262642

Section structured repository metadata, offset —