CD16+ CD163+ monocytes traffic to sites of inflammation in NEC
Download from source ↗Dataset overview
CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants.
Abstract
Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes IL8, CXCL1, CXCL2, CXCL5 and had enrichment of gene sets in pathways involved in chemotaxis, migration, phagocytosis, and reactive oxygen species generation. In summary, we identify a novel subtype of inflammatory monocytes/Mϕ associated with NEC that should be further evaluated as a potential biomarker of surgical NEC and a target for the development of NEC-specific therapeutics.
Study facts
- Organism
- Homo sapiens
- Platform
- 10x Genomics Chromium
- Age group
- paediatric
- Disease groups
- —
- Anatomical sites
- small intestine
Data availability
- Processed matrix
File types
H5ADH5SEURATRDATA
Files and samples
- Fetal small intestine2
- Neonatal small intestine2
- Preterm small intestine2
| Accession | Sample | Tissue | Molecule |
|---|---|---|---|
GSM5379913 |
1100A_Fetal | Fetal small intestine | total RNA |
GSM5379914 |
1102_Fetal | Fetal small intestine | total RNA |
GSM5379915 |
1127Neontal | Neonatal small intestine | total RNA |
GSM5379916 |
1164Neonatal | Neonatal small intestine | total RNA |
GSM5379917 |
1074NEC | Preterm small intestine | total RNA |
GSM5379918 |
1109NEC | Preterm small intestine | total RNA |
Strengths & limitations for reuse
Strengths
- Processed matrices are advertised
Limitations
- Not documented: raw counts are advertised
- Not documented: cell metadata 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 |
single-cell RNA sequencing |
scRNA-seq was performed on a subset of small intestinal mucosa Section |
assay.library_chemistry |
3′ GEM libraries |
3' GEM libraries from 10X Medgenome kit Section |
assay.platform |
10x Genomics Chromium |
using the 10× Genomics Chromium platform Section |
assay.sequencing_type |
scrna_seq |
3' Single cell RNA sequencing Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.age_group |
paediatric from source |
GEO age characteristics: 21 weeks; 21 weeks; 37 weeks; 36 weeks; 31 weeks; 39 weeks Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
data_assets.open_access |
True |
Public on Jun 15 2021 Section |
data_assets.processed_matrix |
True |
GSE178088_cluster3.h5ad.gz Section |
Processing
| Field | Value | Evidence |
|---|---|---|
processing.batch_correction_reported |
True |
The cells from different samples were integrated to minimize the batch effect. Section |
processing.cell_type_annotation_method |
canonical gene expression |
Clusters were identified based on canonical gene expression Section |
processing.normalization_method |
LogNormalize |
The data were normalized using the “LogNormalize” method. Section |
processing.quality_control_reported |
True |
Cells with mitochondria reads >25% or samples where the number of genes was <200 or >7,000 were filtered out. Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.anatomical_sites |
['small intestine'] |
3' Single cell RNA sequencing of viably cryoprserved human small intestinal tissue samples after live/dead selection. Section |
specimens.inflamed_status_available |
True |
"diagnosis": "necrotizing enterocolitis" Section |
specimens.number_of_samples |
6 |
"n_samples": 6 Section |