CDHR5 in intestinal homeostasis

Dataset overview

Participants None

Samples 50

Reuse readiness 5.6/10 evidence-backed score

Defects in microvillus crosslinking sensitize to colitis and inflammatory bowel disease.

Mödl B, Awad M, Zwolanek D, Scharf I, Schwertner K, Milovanovic D, Moser D, Schmidt K, et al. · EMBO reports · 2023

Abstract

Intestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) links the microvilli and is required for proper brush border organization. Whether microvillus crosslinking is involved in the intestinal barrier function or colitis is currently unknown. We investigate the role of microvillus crosslinking in colitis in mice with deletion of the IMAC component CDHR5. Electron microscopy shows pronounced brush border defects in CDHR5-deficient mice. The defects result in severe mucosal damage after exposure to the colitis-inducing agent DSS. DSS increases the permeability of the mucus layer and brings bacteria in direct contact with the disorganized brush border of CDHR5-deficient mice. This correlates with bacterial invasion into the epithelial cell layer which precedes epithelial apoptosis and inflammation. Single-cell RNA sequencing data of patients with ulcerative colitis reveals downregulation of CDHR5 in enterocytes of diseased areas. Our results provide experimental evidence that a combination of microvillus crosslinking defects with increased permeability of the mucus layer sensitizes to inflammatory bowel disease.

doi:10.15252/embr.202357084 ↗ PMID 37691494 ↗ PMC10561180 ↗

Study facts

Organism: —
Platform: Illumina MiSeq
Age group: adult
Disease groups: —
Anatomical sites: —

Data availability

Specific data assets have not been resolved from the source yet — see the source repository below for the full file listing.

Strengths & limitations for reuse

Strengths

Raw reads are advertised
Sample counts are documented

Limitations

Not documented: feature/otu tables are advertised
Not documented: taxonomic tables 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.paired_end`	True	FASTQ reads 1 and 2 were trimmed at 220 nucleotides and 150 nucleotides Section `16S rRNA gene amplicon sequencing and data analysis`, offset 2130
`assay.platform`	Illumina MiSeq from source	ENA instrument_model=Illumina MiSeq Section `ENA study report`, offset —
`assay.primers_reported`	True	using the 16S rRNA gene primers 515F and 806R Section `16S rRNA gene amplicon sequencing and data analysis`, offset 1820
`assay.sequencing_type`	amplicon_16s	16S rRNA gene amplification PCR was performed using the 16S rRNA gene primers 515F and 806R Section `16S rRNA gene amplicon sequencing and data analysis`, offset 1820
`assay.target_region`	V4 (inferred from primers 515F and 806R) inferred	16S rRNA gene amplification PCR was performed using the 16S rRNA gene primers 515F and 806R Section `16S rRNA gene amplicon sequencing and data analysis`, offset 1820

Cohort

Field Value Evidence

Field	Value	Evidence
`cohort.age_group`	adult	Fecal pellets were collected from 8 week old adult mice. Section `16S rRNA gene amplicon sequencing and data analysis`, offset 1030
`cohort.study_design`	longitudinal	A second collection of fecal pellets was performed on day 14 after the recovery period Section `16S rRNA gene amplicon sequencing and data analysis`, offset 1690
`cohort.treatment_exposure_documented`	True	Mice were treated with DSS in sterile autoclaved drinking water... Control mice received sterile autoclaved drinking water throughout the experiment. Section `16S rRNA gene amplicon sequencing and data analysis`, offset 1450

cohort.age_group

adult

Fecal pellets were collected from 8 week old adult mice.

Section 16S rRNA gene amplicon sequencing and data analysis, offset 1030

cohort.study_design

longitudinal

A second collection of fecal pellets was performed on day 14 after the recovery period

Section 16S rRNA gene amplicon sequencing and data analysis, offset 1690

cohort.treatment_exposure_documented

True

Mice were treated with DSS in sterile autoclaved drinking water... Control mice received sterile autoclaved drinking water throughout the experiment.

Section 16S rRNA gene amplicon sequencing and data analysis, offset 1450

Data_Assets

Field Value Evidence

Field	Value	Evidence
`data_assets.open_access`	True	"license": "cc by" Section `publication metadata`, offset —
`data_assets.raw_reads`	True	"run_count": 50, "runs_sample": [{"tax_id": "1441287", "base_count": "14636076", "read_count": "28868" Section `study`, offset —

data_assets.open_access

True

"license": "cc by"

Section publication metadata, offset —

data_assets.raw_reads

True

"run_count": 50, "runs_sample": [{"tax_id": "1441287", "base_count": "14636076", "read_count": "28868"

Section study, offset —

Specimens

Field	Value	Evidence
`specimens.body_site`	fecal	We distinguished between genotypes and sex and included fecal pellets from DSS-treated mice in 16S rRNA gene amplicon-based fecal microbiome analysis. Section `Unchanged fecal microbiome in CDHR5 ∆/∆ mice`, offset —
`specimens.longitudinal_sampling`	True	A second collection of fecal pellets was performed on day 14 after the recovery period Section `16S rRNA gene amplicon sequencing and data analysis`, offset 1690
`specimens.number_of_samples`	50 from source	ENA sample_count=50 Section `ENA study report`, offset —
`specimens.sample_type`	stool	Fecal pellets were collected from 8 week old adult mice. Section `16S rRNA gene amplicon sequencing and data analysis`, offset 1040