Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis
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...
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| Veröffentlicht in: | PLoS biology 2023-05, Vol.21 (5), p.e3002124-e3002124 |
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| creator | Egozi, Adi Olaloye, Oluwabunmi Werner, Lael Silva, Tatiana McCourt, Blake Pierce, Richard W An, Xiaojing Wang, Fujing Chen, Kong Pober, Jordan S Shouval, Dror Itzkovitz, Shalev Konnikova, Liza |
| description | 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. |
| doi_str_mv | 10.1371/journal.pbio.3002124 |
| format | Article |
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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.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.3002124</identifier><identifier>PMID: 37205711</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology and Life Sciences ; Biomarkers ; Dendritic cells ; Development and progression ; Diseases ; Endothelial Cells ; Enterocolitis ; Enterocolitis, Necrotizing - genetics ; Enterocolitis, Neonatal necrotizing ; Enterocolitis, Pseudomembranous ; Epithelial cells ; Epithelium ; Fibroblasts ; Gastrointestinal diseases ; Gene expression ; Gene sequencing ; Health aspects ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infants (Newborn) ; Inflammation ; Intestinal Mucosa ; Intestine ; Intestine, Small ; Intestines ; Ligands ; Lymphocytes ; Lymphocytes T ; Macrophages ; Medicine and Health Sciences ; Methods and Resources ; Morbidity ; Mortality ; Necrosis ; Necrotizing enterocolitis ; Neonates ; Pediatric research ; Premature babies ; Premature birth ; Research and Analysis Methods ; Small intestine ; Surgery ; T cell receptors ; T-cell receptor ; Target recognition ; Transcriptomics ; Villus</subject><ispartof>PLoS biology, 2023-05, Vol.21 (5), p.e3002124-e3002124</ispartof><rights>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.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Egozi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Egozi et al 2023 Egozi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c696t-328c6c578c55cd0b4228eaa2f2d8fc54d4440a78c37ed5611ed959f9b7fe10133</citedby><cites>FETCH-LOGICAL-c696t-328c6c578c55cd0b4228eaa2f2d8fc54d4440a78c37ed5611ed959f9b7fe10133</cites><orcidid>0000-0003-0685-2522 ; 0000-0003-4804-5497</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234541/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234541/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37205711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Egozi, Adi</creatorcontrib><creatorcontrib>Olaloye, Oluwabunmi</creatorcontrib><creatorcontrib>Werner, Lael</creatorcontrib><creatorcontrib>Silva, Tatiana</creatorcontrib><creatorcontrib>McCourt, Blake</creatorcontrib><creatorcontrib>Pierce, Richard W</creatorcontrib><creatorcontrib>An, Xiaojing</creatorcontrib><creatorcontrib>Wang, Fujing</creatorcontrib><creatorcontrib>Chen, Kong</creatorcontrib><creatorcontrib>Pober, Jordan S</creatorcontrib><creatorcontrib>Shouval, Dror</creatorcontrib><creatorcontrib>Itzkovitz, Shalev</creatorcontrib><creatorcontrib>Konnikova, Liza</creatorcontrib><title>Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>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.</description><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Dendritic cells</subject><subject>Development and progression</subject><subject>Diseases</subject><subject>Endothelial Cells</subject><subject>Enterocolitis</subject><subject>Enterocolitis, Necrotizing - genetics</subject><subject>Enterocolitis, Neonatal necrotizing</subject><subject>Enterocolitis, Pseudomembranous</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Fibroblasts</subject><subject>Gastrointestinal diseases</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Infant, Premature</subject><subject>Infants 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atlas of the human neonatal small intestine affected by necrotizing enterocolitis</title><author>Egozi, Adi ; Olaloye, Oluwabunmi ; Werner, Lael ; Silva, Tatiana ; McCourt, Blake ; Pierce, Richard W ; An, Xiaojing ; Wang, Fujing ; Chen, Kong ; Pober, Jordan S ; Shouval, Dror ; Itzkovitz, Shalev ; Konnikova, Liza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c696t-328c6c578c55cd0b4228eaa2f2d8fc54d4440a78c37ed5611ed959f9b7fe10133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Dendritic cells</topic><topic>Development and progression</topic><topic>Diseases</topic><topic>Endothelial Cells</topic><topic>Enterocolitis</topic><topic>Enterocolitis, Necrotizing - genetics</topic><topic>Enterocolitis, Neonatal necrotizing</topic><topic>Enterocolitis, Pseudomembranous</topic><topic>Epithelial 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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. 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| subjects | Biology and Life Sciences Biomarkers Dendritic cells Development and progression Diseases Endothelial Cells Enterocolitis Enterocolitis, Necrotizing - genetics Enterocolitis, Neonatal necrotizing Enterocolitis, Pseudomembranous Epithelial cells Epithelium Fibroblasts Gastrointestinal diseases Gene expression Gene sequencing Health aspects Humans Infant Infant, Newborn Infant, Premature Infants (Newborn) Inflammation Intestinal Mucosa Intestine Intestine, Small Intestines Ligands Lymphocytes Lymphocytes T Macrophages Medicine and Health Sciences Methods and Resources Morbidity Mortality Necrosis Necrotizing enterocolitis Neonates Pediatric research Premature babies Premature birth Research and Analysis Methods Small intestine Surgery T cell receptors T-cell receptor Target recognition Transcriptomics Villus |
| title | Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis |
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