Single-cell RNA sequencing of intestinal immune cells in neonatal necrotizing enterocolitis

Purpose Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC. Methods Using single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four ne...

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Published inPediatric surgery international Vol. 39; no. 1; p. 179
Main Authors Oshima, Kazuo, Hinoki, Akinari, Uchida, Hiroo, Tanaka, Yujiro, Okuno, Yusuke, Go, Yasuhiro, Shirota, Chiyoe, Tainaka, Takahisa, Sumida, Wataru, Yokota, Kazuki, Makita, Satoshi, Takimoto, Aitaro, Kano, Yoko, Sawa, Shinichiro
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 11.04.2023
Springer Nature B.V
Subjects
Dendritic cells
Enterocolitis, Necrotizing - pathology
Gastrointestinal diseases
Gene expression
Genomics
Humans
Immunology
Infant, Newborn
Inflammation
Intestines - pathology
Lymphocytes
Medicine
Medicine & Public Health
Mortality
Necrosis
Newborn babies
Original Article
Pathogenesis
Pediatric Surgery
Pediatrics
Physiology
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
Science
Sequence Analysis, RNA
Signal Transduction
Surgery
Necrotizing enterocolitis
Single-cell sequencing
Gene expression
Intestinal immune cells
Online AccessGet full text
ISSN1437-9813
0179-0358
1437-9813
DOI10.1007/s00383-023-05461-7

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Abstract Purpose Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC. Methods Using single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines. Results In all four cases, major immune cells, such as T cells (15.1–47.7%), B cells (3.1–19.0%), monocytes (16.5–31.2%), macrophages (1.6–17.4%), dendritic cells (2.4–12.2%), and natural killer cells (7.5–12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells. Conclusion Intestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.
AbstractList Purpose Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC. Methods Using single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines. Results In all four cases, major immune cells, such as T cells (15.1–47.7%), B cells (3.1–19.0%), monocytes (16.5–31.2%), macrophages (1.6–17.4%), dendritic cells (2.4–12.2%), and natural killer cells (7.5–12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells. Conclusion Intestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.
PurposeNecrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC.MethodsUsing single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines.ResultsIn all four cases, major immune cells, such as T cells (15.1–47.7%), B cells (3.1–19.0%), monocytes (16.5–31.2%), macrophages (1.6–17.4%), dendritic cells (2.4–12.2%), and natural killer cells (7.5–12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells.ConclusionIntestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.
Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC. Using single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines. In all four cases, major immune cells, such as T cells (15.1-47.7%), B cells (3.1-19.0%), monocytes (16.5-31.2%), macrophages (1.6-17.4%), dendritic cells (2.4-12.2%), and natural killer cells (7.5-12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells. Intestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.
Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC.PURPOSENecrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC.Using single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines.METHODSUsing single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines.In all four cases, major immune cells, such as T cells (15.1-47.7%), B cells (3.1-19.0%), monocytes (16.5-31.2%), macrophages (1.6-17.4%), dendritic cells (2.4-12.2%), and natural killer cells (7.5-12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells.RESULTSIn all four cases, major immune cells, such as T cells (15.1-47.7%), B cells (3.1-19.0%), monocytes (16.5-31.2%), macrophages (1.6-17.4%), dendritic cells (2.4-12.2%), and natural killer cells (7.5-12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells.Intestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.CONCLUSIONIntestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.
ArticleNumber 179
Author Oshima, Kazuo
Tanaka, Yujiro
Kano, Yoko
Shirota, Chiyoe
Tainaka, Takahisa
Uchida, Hiroo
Makita, Satoshi
Hinoki, Akinari
Okuno, Yusuke
Yokota, Kazuki
Go, Yasuhiro
Takimoto, Aitaro
Sumida, Wataru
Sawa, Shinichiro
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  email: sawa@bioreg.kyushu-u.ac.jp
  organization: Division of Mucosal Immunology, Research Center for Systems Immunology, Kyushu University
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crossref_primary_10_3390_life14111510
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Keywords Necrotizing enterocolitis
Single-cell sequencing
Gene expression
Intestinal immune cells
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PublicationDateYYYYMMDD 2023-04-11
PublicationDate_xml – month: 04
  year: 2023
  text: 2023-04-11
  day: 11
PublicationDecade 2020
PublicationPlace Berlin/Heidelberg
PublicationPlace_xml – name: Berlin/Heidelberg
– name: Germany
– name: Berlin
PublicationTitle Pediatric surgery international
PublicationTitleAbbrev Pediatr Surg Int
PublicationTitleAlternate Pediatr Surg Int
PublicationYear 2023
Publisher Springer Berlin Heidelberg
Springer Nature B.V
Publisher_xml – name: Springer Berlin Heidelberg
– name: Springer Nature B.V
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Snippet Purpose Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response...
Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC....
PurposeNecrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to...
Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to...
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StartPage 179
SubjectTerms Dendritic cells
Enterocolitis, Necrotizing - pathology
Gastrointestinal diseases
Gene expression
Genomics
Humans
Immunology
Infant, Newborn
Inflammation
Intestines - pathology
Lymphocytes
Medicine
Medicine & Public Health
Mortality
Necrosis
Newborn babies
Original Article
Pathogenesis
Pediatric Surgery
Pediatrics
Physiology
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
Science
Sequence Analysis, RNA
Signal Transduction
Surgery
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Title Single-cell RNA sequencing of intestinal immune cells in neonatal necrotizing enterocolitis
URI https://link.springer.com/article/10.1007/s00383-023-05461-7
https://www.ncbi.nlm.nih.gov/pubmed/37041419
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