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

doi:10.1371/journal.pbio.3002124

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 journal › Article › peer-review

13 Scopus citations

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 language	English
Article number	e3002124
Journal	PLoS Biology
Volume	21
Issue number	5
DOIs	https://doi.org/10.1371/journal.pbio.3002124
State	Published - May 2023

Funding

Funders	Funder number
Fannie Sherr Fund
Yale Program for the Promotion of Interdisciplinary Science, Binational Science Foundation	R21TR002639, 2019075, R21HD102565, R01AI171980
National Institutes of Health
Yale University	KL2TR001862
National Center for Advancing Translational Sciences
Horizon 2020 Framework Programme	CZF2019-002434, 768956
European Commission
Minerva Foundation
Israel Science Foundation	1486/16
Wolfson Family Charitable Trust
Helen and Martin Kimmel Institute for Stem Cell Research, Weizmann Institute of Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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 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.",

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AU - Olaloye, Oluwabunmi

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AU - McCourt, Blake

AU - Pierce, Richard W.

AU - An, Xiaojing

AU - Wang, Fujing

AU - Chen, Kong

AU - Pober, Jordan S.

AU - Shouval, Dror

AU - Itzkovitz, Shalev

AU - Konnikova, Liza

N1 - Publisher Copyright: © 2023 Egozi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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N2 - 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.

AB - 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.

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

Abstract

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UN SDGs

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