GSE195799
The single-cell landscape of kidney immune cells reveals transcriptional heterogeneity in early diabetic kidney disease
The pathogenesis of diabetic kidney disease (DKD) involves multifactorial processes that converge to initiate and advance the disease. Although DKD is not typically classified as an inflammatory glomerular disease, mounting evidence supports the involvement of renal inflammation as a key contributor in DKD pathogenesis, particularly through macrophages. However, detailed identification and corresponding phenotypic changes in macrophages in DKD remain poorly understood. To capture the gene expression changes in specific macrophage cell subsets in early DKD, we performed a single-cell transcriptomic analysis of CD45-enriched kidney immune cells from type 1 diabetic OVE26 mice at two time points during the disease development and undertook a focused analysis of mononuclear phagocytes (i.e., macrophages and dendritic cells). Our results now show increased resident and infiltrating macrophage subsets in the diabetic kidneys over time, with heightened expression of pro-inflammatory or anti-inflammatory genes in a subset-specific manner. Further analysis of macrophage polarization states in each subset showed changes consistent with the continuum of activation and differentiation states, and their gene expression tended to shift toward undifferentiated phenotypes but with increased M1-like inflammatory phenotypes over time and in the diabetic kidneys. By deconvolution analysis of RNAseq samples of human DKD biopsies and immunostaining, we further confirmed a differential expression of select genes in specific macrophage subsets. Thus, the current study provides a comprehensive analysis of macrophage transcriptomic profiles in early DKD that underscores the dynamic macrophage phenotypes in disease progression. Overall design: To capture the gene expression changes in specific macrophage cell subsets in early DKD, we performed a single-cell transcriptomic analysis of CD45-enriched kidney immune cells from type 1 diabetic OVE26 mice at two time points during the disease development and undertook a focused analysis of mononuclear phagocytes.