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ABSTRACT:
PROVIDER: PRJNA321164 | ENA |
REPOSITORIES: ENA
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Project description:Morphological patterns of Paneth cells are a cellular biomarker in western Crohn’s disease (CD) patients. They integrate genetics and environmental factors, and are associated with outcomes. To broaden the applications of Paneth cell phenotype, identification of novel genetic determinants and clinical validation in other ethnic groups is critical.
2017-08-22 | GSE90102 | GEO
Project description:We previously showed that abnormal morphology phenotype of ileal Paneth cells (Paneth cell phenotype [PCP]; as a surrogate for PC function) correlate with genetics, microbiota compositions, and aggressive outcome in Crohn’s disease (CD) patients. Given the shared genetics and clinical features between CD and ulcerative colitis (UC), we hypothesized that abnormal PCP also negatively modulates UC outcomes. As PCs has the highest density in the ileum, we further hypothesized that abnormal PCP from the terminal ileum could increase the risk of development of pouch complications after UC total colectomy and ileal pouch anal anastomosis (IPAA).
2025-01-01 | E-MTAB-12826 | biostudies-arrayexpress
Project description:Paneth cells, the Microbiome, and Crohn’s Disease Susceptibility
| PRJNA317429 | ENA
Project description:The goal of this project is to find out whether human intestinal IgA1 and IgA2 secretion, transport and reactivity towards the microbiota might be involved in dysbiosis induction during Crohn’s disease and Ulcerative colitis. Mass spectrometry was used to characterize SIgA from Crohn’s disease patient and Ulcerative colitis patient, in term of O- and N-glycosylation in order to study their reverse transcytosis capacity and their role in intestinal inflammation.
2022-06-27 | PXD024060 | Pride
Project description:Single-cell sequencing of intestinal macrophage was peformed with mice colony stimulating factor 1 receptor promoter (CSF1R) positive cells isolated from the 1/3 distal part of the small intestine of male MaFIA mice at postnatal day 17. Intestinal secretory Paneth cells become differentiated during the first two weeks after birth, which coincides with initial gut microbiota exposure. Their number is significantly reduced in cases of necrotizing enterocolitis (NEC), a deadly disease affecting premature infants. Although known to be associated with intestinal immaturity, its underlying disease mechanisms are unclear. Our analysis of mice treated with antibiotics reveals Paneth cell defects, which promote NEC pathogenesis. Our single cell and genetic analyses demonstrate that gut microbiota induces stem cell differentiation into Paneth cells by controlling the number and heterogeneity of macrophage populations that secrete Wnt ligands. Moreover, differentiated M2 macrophages are able to restore Paneth cell differentiation and rescue NEC-like pathology, while the ablation of Paneth cells is sufficient to induce it, leading to lethality. Our work reveals an unexpected requirement for Paneth cell differentiation through the regulation of gut microbiota-macrophage niches in early postnatal development.
2022-12-16 | GSE141561 | GEO
Project description:Nod2 has been extensively characterized as a bacterial sensor that induces an antimicrobial and inflammatory gene expression program. Therefore, it is unclear why Nod2 mutations that disrupt bacterial recognition are paradoxically among the highest risk factors for Crohn’s disease, which involves an exaggerated immune response directed at intestinal bacteria. Previous studies from our lab have shown that mice deficient in Atg16L1, another Crohns disease susceptibility gene, develop abnormalities in Paneth cells, specialized epithelial cells in the small intestine involved in antimicrobial responses. The goal of our study is to determine whether Nod2 deficiency leads to differences in the transcriptional profile of Paneth cells, ultimately leading to small intestinal inflammation. Small intestinal sections (ileum) of 8 week old WT and Nod2-/- mice were fixed in methacarn and embedded in paraffin. The Leica LMD6000 Laser Microdissection system was used to capture crypt base epithelial cells to enrich for Paneth cells. RNA was extracted from these cells, followed by cDNA synthesis and qPCR to confirm enrichment of Paneth cells using unique markers (a-defensins).
2014-07-01 | E-GEOD-58948 | biostudies-arrayexpress
Project description:Crohn’s disease (CD) is associated with multiple Paneth cell dysfunctions such as altered antimicrobial secretion that relies on autophagy - an essential process controlling the turnover of cellular components. Genome-wide association studies have linked CD to mutations in the ATG16l1 gene, encoding an important component of the autophagy machinery. Patients carrying the ATG16l1 CD risk allele have Paneth cell abnormalities, as reproduced in Atg16l1-deficient mouse models. However, the direct effect of the ATG16L1-deficiency and autophagy-impairment in Paneth cells has not been analysed in detail. To investigate this, we generated a mouse model lacking ATG16L1 specifically in intestinal epithelial cells (Atg16l1△IEC) making these cells impaired in autophagy. Using a 3D small intestinal organoid culture model, which we enriched for Paneth cells and compared the proteomic profiles of organoids derived from the wild-type (WT) and the Atg16l1△IEC mice. We used an integrated computational approach combining protein-protein interaction networks, list of proteins potentially targeted by autophagy and functional information on the proteins with altered protein levels to identify the mechanistic link between autophagy-impairment and disrupted cellular process. 198 (70%) of the 284 altered proteins were more abundant in autophagy-impaired organoids than WT organoids that could be due to a reduced protein turnover. Combining the proteomic dataset with the potential target proteins of selective autophagy proteins revealed that 116 (41%) of the differentially abundant proteins could rely on autophagy-mediated turnover. Taken together, our results suggest that proteins with increased levels in autophagy-impaired background require an autophagy-mediated turnover mechanism, and that their altered levels in CD could affect key cellular processes. Consequently, we pointed out the importance of autophagy in controlling the turnover of proteins relevant in key Paneth cell functions such as exocytosis, apoptosis and DNA damage repair. Our study unravels autophagy-dependent cellular processes of Paneth cells that not directly relies on the autophagy process, rather than a selective protein turnover mechanism. The identified proteins and processes open new avenues for targeted, cell type-specific therapeutic interventions in CD.
2019-03-07 | PXD010940 | Pride
Project description:Paneth cells are targets of allo-reactive T cells during acute graft-versus-host disease (GVHD). GVHD-related loss of Paneth cells is connected to intestinal dysbiosis and a decline of antimicrobial peptides. Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone, produced by the intestinal L-cells, that leads to expansion of Paneth cells. Microarray-based analysis of the intestinal tract revealed upregulation of a host-defense gene signature, increased Reg3-γ and Defensin-α-4 in the teduglutide treated group compared to the vehicle treated group. these results indicate that treatment of GVHD mice the GLP-2 analogue, teduglutide, restores intestinal homeostasis with increased Paneth cells and antimicrobial peptides
2023-10-29 | GSE138439 | GEO
Project description:The interpretation of transcriptional profiling studies of intestinal tissue from Crohn’s disease patients and control patients can be confounded by differing proportions of cell subsets (e.g. immune cells) present in these samples. In this study, we aimed to control for cellular composition using standard, archival formalin-fixed, paraffin-embedded (FFPE) tissue specimens from Crohn’s patients (n=36) and controls (n=32) who underwent intestinal resection surgery. This approach allowed us to use the same tissue specimens for histological screening to select study samples with similar cellular composition and for RNA extraction for RNA-seq transcriptional profiling. We hypothesized that this approach would allow us to more clearly identify molecular signatures in ileal tissue that were associated with Crohn’s disease-associated pathological mechanisms.
2018-05-22 | E-MTAB-5790 | biostudies-arrayexpress
Project description:Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells. Experiment Overall Design: 4 Samples: 2 replicates of Atg16-hypomorph Paneth cells and 2 replicates of Wildtype Paneth cells.
2008-11-15 | E-GEOD-13512 | biostudies-arrayexpress