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Related Experiment Video

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Spatial transcriptomics delineates potential differences in intestinal phenotypes of cardiac and classical

Kathryn Y Burge1, Constantin Georgescu2, Hua Zhong1

  • 1Department of Pediatrics, Section of Neonatal-Perinatal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

Iscience
|April 9, 2025
PubMed
Summary

Cardiac NEC and classical NEC, a neonatal gastrointestinal disease, exhibit distinct cellular and molecular differences. Spatial transcriptomics reveals unique immune and epithelial cell pathway variations between these NEC subtypes.

Keywords:
Components of the immune systemDiseaseGastroenterologyPediatricsProteomicsTranscriptomics

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Area of Science:

  • Neonatal Medicine
  • Gastroenterology
  • Genomics

Background:

  • Necrotizing enterocolitis (NEC) is a severe neonatal gastrointestinal disease.
  • Cardiac NEC, a distinct subtype, affects infants with congenital heart disease, differing from classical NEC associated with prematurity.
  • Despite similar symptoms, NEC subtypes may have different causes and presentations.

Purpose of the Study:

  • To compare the ileal spatial transcriptomes of patients with cardiac NEC and classical NEC.
  • To identify differences in cell types, pathways, and networks between NEC subtypes.
  • To elucidate the distinct molecular mechanisms underlying cardiac and classical NEC.

Main Methods:

  • Spatial transcriptomics was employed to analyze ileal tissue samples from patients with cardiac and classical NEC.
  • Cellular populations, including epithelial and immune cells, were segmented and analyzed.
  • Differential gene expression and pathway analysis were performed to identify subtype-specific molecular signatures.

Main Results:

  • Epithelial and immune cells clustered distinctly by cell type and NEC subtype.
  • Functional differences in metabolism and immune cell activation were observed between cardiac and classical NEC.
  • Classical NEC showed dysbiosis-induced inflammation and metabolic acidosis.
  • Cardiac NEC exhibited reduced angiogenesis and endoplasmic reticulum stress-induced apoptosis.

Conclusions:

  • Spatial transcriptomics confirmed distinct pathway and network differences in immune and epithelial cells between cardiac and classical NEC.
  • These findings support the hypothesis that cardiac and classical NEC are etiologically distinct diseases.
  • Understanding these subtype-specific mechanisms is crucial for targeted therapeutic strategies in neonatal NEC.