Transmural Single-Nucleus Transcriptomics Nominates Candidate Disease Programs in Human Necrotizing Enterocolitis

Single-nucleus RNA-seq of 53,735 nuclei from full-thickness human intestine resolves transmural NEC cell types and nominates multicellular disease programs linked to inflammation, stress, and cell death.

• Why it matters: NEC in premature infants involves interacting cell states across intestinal layers, but prior work lacked a cell-type-resolved, transmural map to distinguish disease programs from normal maturation.
• What they did: Full-thickness fetal/prenatal controls, acute NEC, and infant controls were profiled by snRNA-seq, using fetal and infant samples as developmental references, with NEC-versus-infant differential expression, GO, cross-lineage recurrence, and maturity scoring.
• The result: NEC-associated expression shifts recur across lineages, show fetal-like levels for subsets of NEC-regulated genes, and reveal lineage-specific epithelial and non-epithelial program alterations that may support initiation, progression, and resolution.

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