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

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.