NDLI: Single nuclear RNA sequencing of terminal ileum in patients with cirrhosis demonstrates multi-faceted alterations in the intestinal barrier

Content Provider	Springer Nature : BioMed Central
Author	Jiang, Xixian Xu, Ying Fagan, Andrew Patel, Bhaumik Zhou, Huiping Bajaj, Jasmohan S.
Abstract	Patients with cirrhosis have intestinal barrier dysfunction but the role of the individual cell types in human small intestine is unclear. We performed single-nuclear RNA sequencing (snRNAseq) in the pinch biopsies of terminal ileum of four age-matched men [56 years, healthy control, compensated, early (ascites and lactulose use) and advanced decompensated cirrhosis (ascites and rifaximin use)]. Cell type proportions, differential gene expressions, cell-type specific pathway analysis using IPA, and cellular crosstalk dynamics were compared. Stem cells, enterocytes and Paneth cells were lowest in advanced decompensation. Immune cells like naive CD4 + T cells were lowest while ITGAE + cells were highest in advanced decompensation patients. MECOM had lowest expression in stem cells in advanced decompensation. Defensin and mucin sulfation gene (PAPSS2) which can stabilize the mucus barrier expression were lowest while IL1, IL6 and TNF-related genes were significantly upregulated in the enterocytes, goblet, and Paneth cells in decompensated subjects. IPA analysis showed higher inflammatory pathways in enterocytes, stem, goblet, and Paneth cells in decompensated patients. Cellular crosstalk analysis showed that desmosome, protease-activated receptors, and cadherin-catenin complex interactions were most perturbed in decompensated patients. In summary, the snRNAseq of the human terminal ileum in 4 subjects (1 control and three cirrhosis) identified multidimensional alteration in the intestinal barrier with lower stem cells and altered gene expression focused on inflammation, mucin sulfation and cell–cell interactions with cirrhosis decompensation.
Related Links	https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-024-01209-5.pdf
Ending Page	19
Page Count	19
Starting Page	1
File Format	HTM / HTML
ISSN	20453701
DOI	10.1186/s13578-024-01209-5
Journal	Cell & Bioscience
Issue Number	1
Volume Number	14
Language	English
Publisher	BioMed Central
Publisher Date	2024-02-19
Access Restriction	Open
Subject Keyword	Cell Biology Microbiology Stem Cells Neurobiology Proteomics Hepatic encephalopathy Infections Decompensation Mucus layer Rifaximin Defensin
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7/2023

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