Multi-omic profiling reveals epithelial remodeling in necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease predominantly affecting premature infants, characterized by severe intestinal inflammation and tissue necrosis. Despite advances in neonatal care, NEC remains a significant clinical challenge with high mortality and morbidity rates. Understanding the molecular and cellular mechanisms underlying NEC pathogenesis is crucial for developing targeted therapies and improving clinical outcomes. In this study, we utilized a mouse model of NEC induced by hypoxia, formula feeding, and lipopolysaccharide administration to investigate the molecular changes at single-cell resolution. We performed bulk RNA sequencing, single-nucleus RNA sequencing (snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and multiplexed error-robust fluorescence in situ hybridization (MERFISH) spatial transcriptomics on intestinal tissues collected from control and NEC groups at postnatal day 9. Data were analyzed to identify cell populations, epigenetic profiles, and regulatory pathways associated with NEC progression.