Total - Cells of the human intestinal tract mapped across space and time
Download from source ↗Dataset overview
Cells of the human intestinal tract mapped across space and time.
Abstract
The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.
doi:10.1038/s41586-021-03852-1 ↗ PMID 34497389 ↗ PMC8426186 ↗
Study facts
- Organism
- Homo sapiens
- Platform
- 10x Genomics Chromium
- Age group
- mixed
- Disease groups
- —
- Anatomical sites
- cecum mucosa, colonic mucosa, duodenal mucosa, ileal mucosa, jejunal mucosa, mesenteric lymph node, mucosa of appendix, mucosa of ascending colon, mucosa of descending colon, mucosa of rectum, mucosa of sigmoid colon, mucosa of transverse colon
Data availability
- Processed matrix
File types
H5AD
Files and samples
Strengths & limitations for reuse
Strengths
- Raw reads are advertised
- Processed matrices are advertised
- Cell metadata are advertised
- Participant mapping 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 Genomics 5′ gene expression v2 and 3′ gene expression v2 |
Chromium Single Cell 5′ gene expression v.2 (10x Genomics) Section |
assay.platform |
10x Genomics Chromium |
loaded for droplet-based scRNA-seq according to the manufacturer’s protocol for the Chromium Section |
assay.reference_genome |
GRCh38-3.0.0 |
the 10X human transcriptome GRCh38-3.0.0 as the reference Section |
assay.sequencing_type |
scrna_seq from source |
sequencing_type=scrna_seq Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.age_group |
mixed |
in utero development, childhood and adulthood Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
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.participant_metadata |
True from source |
"donor_id": ["T036", "T110", "T161", "T057", "T182", "T044", "T024", "T197", "T160", "T176", "T019", "T202", "T017", "T189", "T203", "A32 (411C)", "A34 (417C)", "A39 (440C)", "A38 (432C)", "A26 (386C)", "F72", "F73", "F78", "F66", "F67", "BRC2258", "BRC2259", "BRC2029", "BRC2026", "BRC2043", "BRC2046", "BRC2049", "BRC2121", "BRC2119", "BRC2133", "BRC2134", "A33 (414C)", "A30 (398B)"] Section |
data_assets.processed_matrix |
True from source |
CELLxGENE dataset exposes H5AD Section |
data_assets.raw_reads |
True from source |
"link_type": "RAW_DATA" Section |
Processing
| Field | Value | Evidence |
|---|---|---|
processing.ambient_rna_correction_reported |
True |
we apply the SoupX algorithm 50 with default parameters and function adjustCounts() to remove ambient mRNA from the count matrix Section |
processing.batch_correction_reported |
True |
Batch correction of fetal and adult datasets was performed with bbknn Section |
processing.cell_type_annotation_method |
Marker-gene expression with Leiden clustering |
cell lineages were annotated on the basis of algorithmically defined marker gene expression for each cluster Section |
processing.doublet_detection_reported |
True |
A Scrublet (v.0.2.1) score cut-off of 0.25 was applied to assist with doublet exclusion Section |
processing.normalization_method |
Per-cell normalization and log transformation |
Gene expression for each cell was normalized and log-transformed Section |
processing.quality_control_reported |
True |
Cells for each dataset were filtered for more than 500 genes and less than 50% mitochondrial reads Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.anatomical_sites |
['cecum mucosa', 'colonic mucosa', 'duodenal mucosa', 'ileal mucosa', 'jejunal mucosa', 'mesenteric lymph node', 'mucosa of appendix', 'mucosa of ascending colon', 'mucosa of descending colon', 'mucosa of rectum', 'mucosa of sigmoid colon', 'mucosa of transverse colon'] from source |
tissues=cecum mucosa, colonic mucosa, duodenal mucosa, ileal mucosa, jejunal mucosa, mesenteric lymph node, mucosa of appendix, mucosa of ascending colon, mucosa of descending colon, mucosa of rectum, mucosa of sigmoid colon, mucosa of transverse colon Section |
specimens.number_of_cells |
428469 from source |
cell_count=428469 Section |
specimens.number_of_samples |
164 |
164 10x Genomics scRNAseq data and 3 10x Visium samples described in this study Section |
specimens.participant_to_sample_mapping_available |
True from source |
"donor_id": ["T036", "T110", "T161", "T057", "T182", "T044", "T024", "T197", "T160", "T176", "T019", "T202", "T017", "T189", "T203", "A32 (411C)", "A34 (417C)", "A39 (440C)", "A38 (432C)", "A26 (386C)", "F72", "F73", "F78", "F66", "F67", "BRC2258", "BRC2259", "BRC2029", "BRC2026", "BRC2043", "BRC2046", "BRC2049", "BRC2121", "BRC2119", "BRC2133", "BRC2134", "A33 (414C)", "A30 (398B)"] Section |