Extended - Large Intestine (adult/pediatric)
Download from source ↗Dataset overview
Single-cell integration reveals metaplasia in inflammatory gut diseases.
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 Genomics Chromium
- Age group
- mixed
- Disease groups
- —
- Anatomical sites
- ascending colon, caecum, colon, colonic epithelium, colonic mucosa, descending colon, epithelium of rectum, lamina propria of mucosa of colon, rectosigmoid junction, rectum, sigmoid colon, transverse colon, vermiform appendix
Data availability
- Processed matrix
- Analysis code
File types
H5AD
Files and samples
Strengths & limitations for reuse
Strengths
- Raw reads are advertised
- 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
| Field | Value | Evidence |
|---|---|---|
assay.assay_type |
10x 3' v2 from source |
assay=10x 3' v2 Section |
assay.library_chemistry |
10x 3' v2; 10x 3' v3; 10x 5' transcription profiling; 10x 5' v1; 10x 5' v2 from source |
10x 3' v2; 10x 3' v3; 10x 5' transcription profiling; 10x 5' v1; 10x 5' v2 Section |
assay.platform |
10x Genomics Chromium |
before proceeding to Chromium 10x Genomics single cell 5′ v2 protocol Section |
assay.reference_genome |
Cell Ranger 2020-A human reference |
Transcriptome reference exactly matching Cell Ranger 2020-A for human was prepared Section |
assay.sequencing_type |
scrna_seq from source |
sequencing_type=scrna_seq Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.age_group |
mixed from source |
Extended - Large Intestine (adult/pediatric) Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
data_assets.analysis_code |
True from source |
Additional code including atlas assembly, annotation and downstream analyses is described in detail throughout the Methods and is available on GitHub Section |
data_assets.cell_metadata |
True from source |
CELLxGENE dataset exposes cell metadata Section |
data_assets.open_access |
True from source |
public CELLxGENE dataset Section |
data_assets.processed_matrix |
True from source |
CELLxGENE dataset exposes H5AD Section |
data_assets.raw_reads |
True from source |
Raw sequencing data for adult samples are available through ArrayExpress with the accession number E-MTAB-14050 Section |
Processing
| Field | Value | Evidence |
|---|---|---|
processing.ambient_rna_correction_reported |
True |
Cellbender v0.2.0 with default parameters was used to remove ambient RNA (soup) Section |
processing.batch_correction_reported |
True |
Healthy/control samples were integrated using scVI Section |
processing.cell_type_annotation_method |
scANVI and weighted k-nearest-neighbour label transfer, with marker-gene refinement |
To refine level 3 annotations on disease cells, we utilized the scArches weighted kNN uncertainty metric Section |
processing.doublet_detection_reported |
True |
Cells were further filtered through automated doublet removal based on scrublet scores Section |
processing.quality_control_reported |
True |
scAutoQC calculated the following metrics Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.anatomical_sites |
['ascending colon', 'caecum', 'colon', 'colonic epithelium', 'colonic mucosa', 'descending colon', 'epithelium of rectum', 'lamina propria of mucosa of colon', 'rectosigmoid junction', 'rectum', 'sigmoid colon', 'transverse colon', 'vermiform appendix'] from source |
tissues=ascending colon, caecum, colon, colonic epithelium, colonic mucosa, descending colon, epithelium of rectum, lamina propria of mucosa of colon, rectosigmoid junction, rectum, sigmoid colon, transverse colon, vermiform appendix Section |
specimens.number_of_cells |
96675 from source |
cell_count=96675 Section |