Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis

Adi Egozi, Oluwabunmi Olaloye, Lael Werner, Tatiana Silva, Blake McCourt, Richard W. Pierce, Xiaojing An, Fujing Wang, Kong Chen, Jordan S. Pober, Dror Shouval, Shalev Itzkovitz*, Liza Konnikova*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Necrotizing enterocolitis (NEC) is a gastrointestinal complication of premature infants with high rates of morbidity and mortality. A comprehensive view of the cellular changes and aberrant interactions that underlie NEC is lacking. This study aimed at filling in this gap. We combine single-cell RNA sequencing (scRNAseq), T-cell receptor beta (TCRβ) analysis, bulk transcriptomics, and imaging to characterize cell identities, interactions, and zonal changes in NEC. We find an abundance of proinflammatory macrophages, fibroblasts, endothelial cells as well as T cells that exhibit increased TCRβ clonal expansion. Villus tip epithelial cells are reduced in NEC and the remaining epithelial cells up-regulate proinflammatory genes. We establish a detailed map of aberrant epithelial–mesenchymal–immune interactions that are associated with inflammation in NEC mucosa. Our analyses highlight the cellular dysregulations of NEC-associated intestinal tissue and identify potential targets for biomarker discovery and therapeutics.

Original languageEnglish
Article numbere3002124
JournalPLoS Biology
Volume21
Issue number5
DOIs
StatePublished - May 2023

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