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

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. Overall design: In this study, we determined the state of Mo in the setting of diabetes with and without DGE in a STZ-induced-diabetes mouse model using cytometry by time-of-flight (CyTOF) and computational analysis.