Single cell atlas of the neonatal small intestine with necrotizing enterocolitis

Egozi, A.; Olaloye, O.; Werner, L.; Silva, T.; McCourt, B.; Pierce, R.; An, X.; Wang, F.; Chen, K.; Pober, J.; Shouval, D.; Itzkovitz, S.; Konnikova, L.

doi:10.1101/2022.03.01.482508

bioRxiv · 10.1101/2022.03.01.482508

Single cell atlas of the neonatal small intestine with necrotizing enterocolitis

Egozi, A.·Olaloye, O.·Werner, L.·Silva, T.·McCourt, B.·Pierce, R.·An, X.·Wang, F.·Chen, K.·Pober, J.·Shouval, D.·Itzkovitz, S.·Konnikova, L.

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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 this disease is lacking. Here, we combine single cell RNA sequencing, T Cell Receptor beta (TCR{beta}) analysis, bulk transcriptomics, and imaging to characterize cell identities, interactions and zonal changes in NEC. We find that inflammatory macrophages are abundant in NEC and that T cells exhibit increased expression of inflammatory genes and cytokines accompanied by an increase in TCR{beta} clonal expansion. Fibroblasts and endothelial cells increase in proportion and exhibit a switch to an activated pro-inflammatory state. Villus tip epithelial cell identity is substantially reduced in NEC and the remaining epithelial cells up-regulate pro-inflammatory genes. We establish a detailed map of aberrant epithelial-mesenchymal-immune interactions that may be driving inflammation in NEC mucosa. Our analyses highlight the cellular changes underlying NEC disease pathogenesis and identify potential targets for biomarker discovery and therapeutics.

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Egozi, A., Olaloye, O., Werner, L., Silva, T., McCourt, B., Pierce, R., An, X., Wang, F., Chen, K., Pober, J., Shouval, D., Itzkovitz, S., Konnikova, L.. 2022-03-02. Single cell atlas of the neonatal small intestine with necrotizing enterocolitis. https://doi.org/10.1101/2022.03.01.482508

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