Figure 1. Renin^null cells have different transcriptomic profiles.

(A) Pathological findings of Ren1^c-KO mice. Immunohistochemistry for α-SMA showed hypertrophic arterioles in Ren1^c-KO mouse kidneys. Scale bars: 20 μm. Kidney sections from Ren1^c-KO Ren1^c-Cre Confetti mice showed multiple colors in the hypertrophic arterioles, suggesting the multiclonality of Renin^null cells. Scale bars: 20 μm. Left: WT mice showed normal architecture of periglomerular arterioles with a single layer of smooth muscle cells (SMCs). Right: Ren1^c-KO mice showed concentric hypertrophy of arteriolar smooth muscle. Scale bars: 10 μm. (B) Schematic of scRNA-Seq of WT renin cells and Renin^null cells. Ren1^c-YFP mice have a transgene consisting of the YFP genes driven by the Ren1^c gene regulatory region. YFP-positive kidney cells from Ren1^c+/+ Ren1^c-YFP mice and Ren1^c–/– Ren1^c-YFP mice were isolated by FACS. Single cells were captured with the Fluidigm C1 System, and scRNA-Seq was performed. Scale bars: 50 μm. (C) The UMAP with all the cells after normalization. (D) Volcano plot showing the differentially expressed genes between WT renin cells and Renin^null cells. (E) Heatmap analysis with differentially expressed genes showed a clear separation of WT renin cells and Renin^null cells. (F) The 10 most enriched categories identified by GO analysis on genes higher in WT renin cells (red) and genes higher in Renin^null cells (blue). (G) Venn diagram showing differentially expressed genes. α-SMA, α–smooth muscle actin; EM, electron microscopy; FACS, fluorescence-activated cell sorting; GO, Gene Ontology; Ren1^c-KO, Ren1^c gene knockout; scRNA-Seq, single-cell RNA sequencing; UMAP, uniform manifold approximation and projection; WT, wild-type.