Foundry120 atlas

← IBD spatial transcriptomics

Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients with Ulcerative Colitis

Download from source ↗

Dataset overview

Participants 15
Samples 23
Reuse readiness 6.9/10 evidence-backed score

Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis.

Lyu D, Kou G, Li S, Li L, Li B, Zhou R, Yang X, Tian W, et al. · Frontiers in cell and developmental biology · 2022

Abstract

As a major component of the enteroendocrine system, enterochromaffin (EC) cells play a key role in ulcerative colitis (UC). However, the scarcity of EC cells has limited the investigation of their function. In this study, we applied digital spatial profiling to acquire transcriptomic data for EC cells and other epithelial cells from colonoscopic biopsy samples from eight patients with UC and seven healthy controls. Differential expression analysis, gene set enrichment analysis, and weighted gene coexpression network analysis were performed to identify differentially expressed genes and pathways and coexpression networks. Results were validated using an online dataset obtained by single-cell RNA sequencing, along with immunofluorescence staining and quantitative real-time PCR. In healthy participants, 10 genes were significantly enriched in EC cells, functionally concentrated in protein and bioamine synthesis. A coexpression network containing 17 hub genes, including <i>TPH1</i>, <i>CHGA</i>, and <i>GCLC</i>, was identified in EC cells. In patients with UC, EC cells gained increased capacity for protein synthesis, along with novel immunological functions such as antigen processing and presentation, whereas chemical sensation was downregulated. The specific expression of <i>CHGB</i> and <i>RGS2</i> in EC cells was confirmed by immunofluorescence staining. Our results illuminate the transcriptional signatures of EC cells in the human colon. EC cells' newly observed functional shift from sensation to secretion and immunity indicates their pivotal role in UC.

doi:10.3389/fcell.2022.841090 ↗ PMID 35465329 ↗ PMC9023741 ↗

Study facts

Organism
Homo sapiens
Platform
NanoString GeoMx Digital Spatial Profiler
Age group
—
Disease groups
Non-IBD controls, Ulcerative colitis
Anatomical sites
Ulcerative Colitis, Control

Data availability

  • Raw counts
  • Processed matrix

File types CSV

Strengths & limitations for reuse

Strengths

  • Raw counts are advertised
  • Processed matrices are advertised
  • Participant counts are documented

Limitations

  • Not documented: spatial coordinates are advertised
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.number_of_cells_or_spots 23
"sample_count": 23

Section geo_family_soft, offset 3300
assay.panel_size 18676
probes for 18,676 endogenous targets

Section Materials and Methods > In situ Hybridization and Digital Spatial Profiling, offset 10600
assay.platform NanoString GeoMx Digital Spatial Profiler
slides were loaded into a GeoMX Digital Spatial Profiler (NanoString) and scanned

Section Materials and Methods > In situ Hybridization and Digital Spatial Profiling, offset 11100
assay.reference_genome GRCh38 from source
GRCh38

Section GEO family SOFT, offset —
assay.resolution spot inferred
each ROI covering either an EPCAM+ 5-HT+ area or an EPCAM+ 5-HT− area

Section Materials and Methods > In situ Hybridization and Digital Spatial Profiling, offset 11300
assay.segmentation_method Immunofluorescence-guided ROI selection using EPCAM, 5-HT and nuclear Syto 13 staining
regions of interest (ROIs) were selected on the basis of immunofluorescence signal

Section Materials and Methods > In situ Hybridization and Digital Spatial Profiling, offset 10950
assay.sequencing_based True from source
GEO assay type/library strategy: OTHER

Section GEO family SOFT, offset —

Cohort

FieldValueEvidence
cohort.disease_activity_metadata_available True
A total of 42 patients diagnosed with active UC and 36 healthy control participants

Section Materials and Methods > Participants, offset 7800
cohort.non_ibd_controls 7
from 8 UC patients and 7 healthy controls

Section geo_record_summary, offset 1050
cohort.study_design cross_sectional inferred
acquire transcriptomic data ... from 8 UC patients and 7 healthy controls

Section geo_record_summary, offset 1050
cohort.total_participants 15 inferred
from 8 UC patients and 7 healthy controls

Section geo_record_summary, offset 1050
cohort.ulcerative_colitis_participants 8
from 8 UC patients and 7 healthy controls

Section geo_record_summary, offset 1050

Data_Assets

FieldValueEvidence
data_assets.file_manifest True from source
Supplementary files enumerated in family SOFT ()

Section GEO family SOFT, offset —
data_assets.open_access True
"isOpenAccess": "Y"

Section europepmc_record, offset 5800
data_assets.participant_metadata True
"diagnosis": {"Ulcerative colitis": 12, "Healthy": 11}

Section geo_family_soft, offset 4200
data_assets.processed_matrix True
GSE183853_Normalized_Data.csv.gz

Section geo_document, offset 40
data_assets.raw_counts True
GSE183853_Initial_Dataset.csv.gz

Section geo_document, offset —
data_assets.sample_metadata True
"sample_count": 23

Section geo_family_soft, offset 3300

Specimens

FieldValueEvidence
specimens.anatomical_sites ['Ulcerative Colitis', 'Control'] from source
GEO sample source names: Ulcerative Colitis; Control

Section GEO family SOFT, offset —
specimens.inflamed_status_available True
Biopsy specimens were collected from the inflamed mucosa of the sigmoid colon or rectum

Section Materials and Methods > Sample Preparation and Tissue Microarray Construction, offset 9000
specimens.number_of_samples 23 computed
23 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
specimens.preservation_method 4% neutral buffered polyformaldehyde fixation and paraffin embedding
immediately fixed in 4% neutral buffered polyformaldehyde overnight. After dehydration and embedding

Section Materials and Methods > Sample Preparation and Tissue Microarray Construction, offset 9050
specimens.specimen_type biopsy
Biopsy specimens of patients with UC were collected from the mucosa

Section Materials and Methods > Participants, offset 7900