Mass Cytometric Analysis of Circulating Monocyte Subsets in a Murine Model of Diabetic Gastroparesis.

Abstract

Circulating monocytes (Mo) are precursors to a subset of gastric resident-muscularis macrophages. Changes in muscularis-macrophages (MMs) result in delayed gastric emptying (DGE) in diabetic gastroparesis. However, the dynamics of Mo in the development of DGE in an animal model are unknown. 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 (Ly6C^hiCCR2^hi-intCD62L^hiLy6G^hiCD45R^hiMERTK^hiintLGALS3^intCD14^intCX3CR1^lowSiglec-H^int-low) 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 levels of chemokine receptor Ccr2 and its ligand Ccl2, suggesting increased trafficking of classical-Mo. These findings establish a link between two CMo-like clusters and the development of DGE phenotype and contribute to better understanding of the heterogenicity of the Mo-population.