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Single cell gene expression analysis of mouse CD45.2+ intraepithelial lymphocyes (IELs) from stomach, small intestine, cecum and colon.

ABSTRACT: To understand the diversity of IELs in the gastrointestinal tract, CD45.2+ IELs from stomach, small intestine, cecum and colon of C57BL/6 mice were isolated for single cell RNA sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE202690 | GEO | 2023/10/06

REPOSITORIES: GEO

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Single cell gene expression analysis of mouse CD45.2+ intraepithelial lymphocyes (IELs) from stomach, small intestine, cecum and colon.

Project description:Single cell gene expression analysis of mouse CD45.2+ intraepithelial lymphocyes (IELs) from stomach, small intestine, cecum and colon.

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Gene expressions of TCRαβ+ CD8αα+ intraepithelial lymphocyte (IELs) in the small intestine with or without Rbpj gene

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Examining the role of murine norovirus (MNV)-infection on intraepithelial lymphocytes (IELs).

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RNA libraries of sorted CD8+ memory T cells from the spleen and RNA libraries of sorted IELs from the small intestine of C57BL/6J mice

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Project description:The nature of gut intraepithelial lymphocytes lacking antigen receptors remains controversial. Herein we showed that, in humans and in mice, innate intestinal intraepithelial lymphocytes expressing intracellular CD3 (iCD3+ innate IELs) differentiate along an Id2 transcription factor (TF)-independent pathway in response to TF NOTCH1, interleukin 15 (IL-15) and Granzyme B signals. In NOTCH1-activated human hematopoietic precursors, IL-15 induced Granzyme B, which cleaved NOTCH1 into a peptide lacking transcriptional activity. As a result, NOTCH1 target genes indispensable for T cell differentiation were silenced and precursors were reprogrammed into innate cells with T cell marks including intracellular CD3 and T cell rearrangements. This pathway was operational in vivo in the mouse gut and led to the local differentiation of iCD3+ innate IELs from a bone marrow-derived precursor. In a subset of celiac patients, iCD3+ innate IELs with gain-of-function mutations in Janus kinase 1 or Signal transducer and activator of transcription 3 displayed enhanced response to IL-15 and acquired a selective advantage that favored clonal expansion and transformation into lymphoma. Overall we characterized gut T cell-like innate IELs, deciphered their pathway of differentiation, and showed their malignant transformation in celiac disease.

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Gene expression assessed by genome wide hybridization bead array in intraepithelial lymphocytes (IELs) isolated from small intestinal biopsies of celiac disease patients with active disease and clinical controls

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AP-1B regulates interaction between intraepithelial lymphocyte-epithelial cell in the intestine

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Label-free and targeted mass tandem (TMT-labelled) global proteomic analyses on mucus from the stomach, small and large intestine of pigLabel-free and targeted mass tandem (TMT-labelled) global proteomic analyses on mucus from the stomach, small and large intestine of pig

Project description:The gastrointestinal mucus is a hydrogel that lines the luminal side of the gastrointestinal epithelium, offering barrier protection from pathogens and lubrication of the intraluminal contents. These barrier properties likewise affect nutrients and drugs that need to penetrate the mucus to reach the epithelium prior to absorption. In order to assess the potential impact of the mucus on drug absorption, we need information about the nature of the gastrointestinal mucus. Today, most of the relevant available literature is mainly derived from rodent studies. In this work, we used a larger animal species; the pig model to characterize the mucus throughout the length of the gastrointestinal tract. This is the first report of the physiological properties (physical appearance, pH and water content), composition and structural profiling of the porcine gastrointestinal mucus. Gastrointestinal mucus was collected from the stomach, small intestine (duodenum, jejunum, ileum) and large intestine (cecum, proximal and distal colon) from slaughtered pigs. The composition of the mucus was characterized both with labelfree and TMT proteomics, with lipidomics and metabolomics. The structural profiling was determined with rheological measurements and cryo-Scanning Electron Microscopy. These findings allow for direct comparisons between the characteristics of mucus from various segments and can be further utilized to improve our understanding of the role of the mucus on region dependent drug absorption. Additionally, the present work is expected to contribute to the assessment of the porcine model as a preclinical species in the drug development process.

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