Fig. 6: Single cell RNA-seq studies of antibody-mediated Pdgfd inhibition in the mouse atherosclerosis model.

a Schematic of experimental design showing that SMC-specific lineage tracing wildtype mice were treated with tamoxifen at 8 weeks of age and tissues harvested after 8 and 16 weeks of high fat diet. Blocking Pdgfd antibody or isotype control antibody administration,10 mg/kg subcutaneously twice weekly, was initiated at 11 weeks and continued until animals were sacrificed after either 8 weeks exposure to the diet (5 weeks antibody) or 16 weeks diet (13 weeks antibody), and scRNAseq conducted at these timepoints. Created with BioRender.com. b Heatmap showing gene expression changes after 5 weeks of antibody treatment. The Fblst-1 cluster shows early downregulation of Pdgfd-regulated genes, and FMC and CMC cluster cells beginning to show evidence of upregulation of these genes as the SMC lineage cells are undergoing phenotypic transition in the developing lesion. Yellow color indicates differential downregulated genes, genes in red text reside in window of lead SNP ± 500 kilobases. c Heatmap showing decreases in Pdgfd regulated genes across different cell clusters in targeted animals compared to controls. Yellow color indicates differential downregulated genes, genes in red text reside in window of lead SNP ± 500 kilobases. d Bar plot presenting the average percentage of lineage traced cells and e non-lineage traced cells in Ctl antibody and Pdgfd blocking antibody groups.