Ly6ChiCD62LhiLy6GhiCx3CR1low Circulating Monocyte subsets are altered in a Murine Diabetic Gastroparesis Model
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PROVIDER: PRJNA1195975 | ENA |
REPOSITORIES: ENA
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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.
2025-01-06 | GSE283889 | GEO
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
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.
2019-09-15 | GSE130672 | GEO
Project description:Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis
| PRJNA540941 | ENA
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.
2020-12-31 | GSE139577 | GEO
Project description:Monocytes and their lineage descendants serve as a central defense system against infection and injury but if uncontrolled can also promote an excessive pathological inflammatory response. Therefore a current research goal is to understand how the organism controls the number and function of monocytes and how these variables can be tailored in therapy. Considering the evidence that monocytes are heterogeneous and exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. Here we investigate the differential expression of mRNA among murine steady-state monocyte subsets. Blood was drawn from healthy C57BL/6 donors. For each biological replicate 1000 monocytes of the Ly-6Chi and Ly-6Clo phenotype were isolated from the blood sample through fluorescence activated cell sorting.
2012-04-05 | E-GEOD-32364 | biostudies-arrayexpress
Project description:Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of body's innate immune system, however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. Here, scRNA-seq was performed to reveal monocytes heterogeneity in healthy and KD infants. Circulating monocytes were separated from peripheral blood and scRNA-seq was used to transcriptionally profile the monocytes in both healthy and KD infants. Four monocyte subsets are identified in infants, in which three clusters are mainly CD14+CD16- monocytes and one cluster is mainly CD14-CD16+ monocytes. The four monocyte subsets possess different biological functions and represent a relatively linear differentiation. CD14+ monocyte subsets in KD are distinct from that of healthy infants, including one subset expressing FOLR3, S100A12 and IL1R2 and the other expressing MT-TN specifically. Moreover, the CD14+ monocyte subsets in KD are poorly differentiated, and their functions mainly involve neutrophil activation. In conclusion, a relatively comprehensive map of circulating monocyte subsets was plotted for the first time in healthy infants. CD14+ monocyte subsets that are distinct from healthy infants were revealed in KD, which may serve as a target for KD treatment in the future.
2021-03-24 | GSE152450 | GEO
Project description:Monocytes and their lineage descendants serve as a central defense system against infection and injury but if uncontrolled can also promote an excessive pathological inflammatory response. Therefore a current research goal is to understand how the organism controls the number and function of monocytes and how these variables can be tailored in therapy. Considering the evidence that monocytes are heterogeneous and exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. Here we investigate the differential expression of mRNA among murine steady-state monocyte subsets.
2012-04-06 | GSE32364 | GEO
Project description:Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of monocyte subsets associated with active versus latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on classical (CD14+CD16-), intermediate (CD14+CD16+) and non-classical (CD14-CD16+) monocytes isolated from individuals with active TB (at diagnosis and 2 months post treatment), latent TB, as well as from TB negative healthy controls. Overall, we found specific gene signatures for each monocyte subset that could successfully discriminate between individuals with active TB at diagnosis, treated active TB, latent TB and healthy controls.
2023-01-03 | GSE185372 | GEO
Project description:Transcriptomic profile of circulating monocyte subsets in active versus latent tuberculosis
| PRJNA768837 | ENA