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.
Funder
Yale University
Patterson Mentored Trust Research award
National Center for Advancing Translational Science
National Institute of Health
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
European Union’s Horizon 2020 research
Chan Zuckerberg Initiative
Publisher
Public Library of Science (PLoS)
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience
Cited by
4 articles.
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