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Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with gastroparesis

ABSTRACT: The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in gastroparesis and obesity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129398 | GEO | 2019/06/21

REPOSITORIES: GEO

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Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis.

Project description: Not available

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Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with gastroparesis

Project description:Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with gastroparesis

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Changes in Muscularis Macrophage Populations in Diabetes

Project description:Macrophages in the muscle layers of the stomach (Muscularis Macrophages - MMs) play a crucial role in regulating gastric motility and immune homeostasis by interacting with cells in their shared environment and play a central role in development of diabetic gastroparesis, a diabetic complication. The lack of knowledge of the subtypes of murine MMs that reside in the stomach limits a comprehensive understanding of their function and their involvement in disease development.

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RNA seq in human gastroparesis

Project description:Both diabetic and idiopathic gastroparesis have unique and overlapping changes in the transcriptome. Immune signaling predominately plays a role in the pathogenesis of gastroparesis.

2018-09-03 | GSE115601 | GEO

miRNA sequencing profile of human plasma samples from healthy, diabetic, and gastroparesis patients

Project description:We report the high-throughput miRNA sequencing of plasma isolated from human patients with type 2 diabetes & gastroparesis, idiopathic gastroparesis alone, and healthy control patients.

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Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis

Project description:Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from gastric tissue of 20 subjects (13 controls, 7 IG). Canonical markers, differential expression, and signalling were determined. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes (FDR<0.05). In IG, MM had decreased expression of tissue-protective and microglial genes and increased expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis to inflammatory sites were upregulated. In summary, human gastric muscle has a rich representation of immune cells; and IG patients demonstrate a higher expression of pro-inflammatory genes and signaling in MM. These data further link immune dysregulation to pathophysiology of gastroparesis.

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Ly6ChiCD62LhiLy6GhiCx3CR1low Circulating Monocyte subsets are altered in a Murine Diabetic Gastroparesis Model

Project description:Circulating monocytes (Mo) are precursors to a subset of gastric resident-muscularis-macrophages (MMs). Changes in MMs are associated with delayed gastric emptying (DGE) in diabetic gastroparesis. Investigating the dynamics of Mo in an animal model of DGE using CyTOF and computational approaches, we show a high heterogeneity within the Mo-population. In DGE mice, via unbiased clustering we identified two reduced Mo clusters which exhibit migratory phenotype (Ly6ChiCD62LhiLy6GhiCD45RhiCCR2hi-intMERTEKhi-intCx3CR1low) resembling classical-Mo (CMo-like). All markers enriched in these clusters are known to regulate cell differentiation, proliferation, adhesion, and migration. Trajectory inference analysis predicted these Mo as precursors to subsequent Mo-lineages. In gastric muscle tissue, we demonstrated an increase in the gene expression level of chemokine receptor Ccr2, suggesting possibly increased trafficking of classical monocytes. These findings contribute to better understanding of the heterogenicity of the Mo-population and establish a link between two CMo-like clusters and the development of DGE phenotype.

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Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

Project description:Background: Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in animal models of diabetes. Human studies have also revealed loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages in full thickness gastric biopsies from gastroparesis patients. Aim: We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in full thickness gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying and symptoms. Methods: Full-thickness gastric antrum biopsies were obtained from nine DG, seven IG patients and five non-diabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1300 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity Pathway Analysis and correlations were carried out. Multiple-testing corrected p-values <0.05 were considered statistically significant. Results: 73 proteins were differentially expressed in DG, 132 proteins in IG and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway (DG FDR: 7.9x10-9; IG FDR: 6.3x10-12). In DG, properdin expression correlated with GCSI-bloating (r: -0.99, FDR: 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C zeta type and complement C2 correlated with 4 hr gastric retention (r: -0.97, FDR: 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Conclusions: Protein expression changes suggest a central role of macrophage-driven immune dysregulation and complement activation in gastroparesis.

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RNA seq in human gastroparesis

Project description:RNA seq in human gastroparesis

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Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

Project description:Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

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