Foundry120 atlas

← IBD single-cell transcriptomics

Paediatric Human Gut (4-14y)

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Dataset overview

Participants 15
Samples 15
Reuse readiness 9.0/10 evidence-backed score

Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn's Disease.

Elmentaite R, Ross ADB, Roberts K, James KR, Ortmann D, Gomes T, Nayak K, Tuck L, et al. · Developmental cell · 2020

Abstract

Human gut development requires the orchestrated interaction of differentiating cell types. Here, we generate an in-depth single-cell map of the developing human intestine at 6-10 weeks post-conception. Our analysis reveals the transcriptional profile of cycling epithelial precursor cells; distinct from LGR5-expressing cells. We propose that these cells may contribute to differentiated cell subsets via the generation of LGR5-expressing stem cells and receive signals from surrounding mesenchymal cells. Furthermore, we draw parallels between the transcriptomes of ex vivo tissues and in vitro fetal organoids, revealing the maturation of organoid cultures in a dish. Lastly, we compare scRNA-seq profiles from pediatric Crohn's disease epithelium alongside matched healthy controls to reveal disease-associated changes in the epithelial composition. Contrasting these with the fetal profiles reveals the re-activation of fetal transcription factors in Crohn's disease. Our study provides a resource available at www.gutcellatlas.org, and underscores the importance of unraveling fetal development in understanding disease.

doi:10.1016/j.devcel.2020.11.010 ↗ PMID 33290721 ↗ PMC7762816 ↗

Study facts

Organism
Homo sapiens
Platform
10x Genomics Chromium
Age group
paediatric
Disease groups
—
Anatomical sites
ileal mucosa

Data availability

  • Processed matrix
  • Analysis code

File types H5AD

Strengths & limitations for reuse

Strengths

  • Raw reads are advertised
  • Processed matrices are advertised
  • Cell metadata are advertised
  • Analysis code is available
  • Participant mapping is available
  • Participant counts are documented

Limitations

  • Not documented: raw counts are advertised
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' v2 from source
assay=10x 3' v2

Section structured repository metadata, offset —
assay.library_chemistry 10x Genomics Single Cell 3′ v2
Chromium Single Cell 3’ Library & Gel Bead Kit v2

Section Key Resources Table, offset —
assay.platform 10x Genomics Chromium
loaded onto a separate channel of a Chromium 10x Genomics single cell 3’v2 library chip

Section Method Details—Single-cell RNA-sequencing, offset —
assay.reference_genome GRCh38-1.2.0
aligned to the GRCh38-1.2.0 human reference transcriptome

Section STAR Methods—Processing FASTQ Files and Quality Control, offset —
assay.sequencing_type scrna_seq from source
sequencing_type=scrna_seq

Section structured repository metadata, offset —

Cohort

FieldValueEvidence
cohort.age_group paediatric from source
Paediatric Human Gut (4-14y)

Section dataset.title, offset —
cohort.crohns_disease_participants 7
we performed scRNA-seq terminal ileum biopsies obtained from children newly diagnosed with CD (n = 7).

Section Results—Parallels between Fetal and Inflamed Epithelium in Crohn’s Disease Patients, offset —
cohort.non_ibd_controls 8
mucosal biopsies from the small bowel of healthy children aged between 4 and 12 years ... (n = 8)

Section Results—Single-Cell Map of the Human Embryonic, Fetal and Pediatric Gut, offset —
cohort.total_participants 15 computed
healthy children aged between 4 and 12 years (n = 8) ... children newly diagnosed with CD (n = 7)

Section Results—Single-Cell Map of the Human Embryonic, Fetal and Pediatric Gut, offset —

Data_Assets

FieldValueEvidence
data_assets.analysis_code True
The code generated during this study will be available at Github https://github.com/Raselel/DevCell_GutAtlas/

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

Section structured repository metadata, 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 —
data_assets.raw_reads True
The accession number for the raw sequencing data reported in this paper is E-MTAB-8901

Section Data and Code Availability, offset —

Processing

FieldValueEvidence
processing.batch_correction_reported True
we used batch balanced k nearest neighbour (BBKNN) method

Section STAR Methods—Clustering, Visualisation and Cell Annotation, offset —
processing.cell_type_annotation_method literature marker genes combined with differentially expressed genes
Clusters were annotated using markers genes found in the literature in combination with differentially expressed genes

Section STAR Methods—Clustering, Visualisation and Cell Annotation, offset —
processing.doublet_detection_reported True
All 10x runs were processed using Scrublet doublet detection pipeline

Section STAR Methods—Doublet Removal, offset —
processing.normalization_method total UMI per cell normalization followed by log transformation
we normalised expression values for total UMIs per cell and log transformed the counts

Section STAR Methods—Processing FASTQ Files and Quality Control, offset —
processing.quality_control_reported True
11,302 pediatric terminal ileal (n = 8) cells passed quality control and doublet exclusion criteria

Section Results—Single-Cell Map of the Human Embryonic, Fetal and Pediatric Gut, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['ileal mucosa'] from source
tissues=ileal mucosa

Section structured repository metadata, offset —
specimens.number_of_cells 22502 from source
cell_count=22502

Section structured repository metadata, offset —
specimens.number_of_samples 15
15 gene expression matrices of healthy and CD paediatric biopsy samples were merged

Section Processing FASTQ Files and Quality Control, offset —
specimens.participant_to_sample_mapping_available True from source
"donor_id": ["T017", "T019", "T024", "T036", "T44", "T057", "T110POS", "T160", "T161", "T176", "T182", "T189", "T197", "T203", "T202"]

Section dataset.donor_id, offset —
specimens.specimen_type biopsy
Human intestinal mucosal biopsies were obtained from patients undergoing colonoscopy

Section Experimental Model and Subject Details—Fetal and Paediatric Tissue Sampling, offset —