Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis
Open Access
- 19 May 2023
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Biology
- Vol. 21 (5), e3002124
- https://doi.org/10.1371/journal.pbio.3002124
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.Funding Information
- Yale University
- Patterson Mentored Trust Research award
- National Center for Advancing Translational Science (KL2TR001862)
- Yale University (2019075)
- National Institute of Health (R21TR002639, R21HD102565,R01AI171980)
- Wolfson Family Charitable Trust
- Edmond de Rothschild Foundations
- Fannie Sherr Fund
- Dr. Beth Rom-Rymer Stem Cell Research Fund
- Helen and Martin Kimmel Institute for Stem Cell Research
- Richard F. Goodman Yale/Weizmann Exchange Program
- Minerva Foundation
- Israel Science Foundation (1486/16)
- European Union’s Horizon 2020 research (768956)
- Chan Zuckerberg Initiative (CZF2019‐002434)
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