Mapping the Single Cell Transcriptomic Response of Murine Diabetic Kidney Disease to Therapies

In this study, we utilized the db/db, uninephrectomy and renin-hypertension mouse model. We compared vehicle to ACE inhibitor, Rosiglitizone, SGLT2 inhibitor, ACEi + Rosiglitizone and ACEi + SGLT2i at two time points (2 days and 2 weeks). We generated snRNA-seq datasets from all groups comprising nearly 1 million cells. Analysis of the resulting atlas revealed that the different medications affected strikingly different cell types. Combination therapy had the largest effects, but these effects were also largely non-overlapping. This study highlights the cellular complexity of diabetic nephropathy and the effects of different classes of therapy. The results support the development of combination therapies since different drug classes target different cell types in kidney. Overall design: We employed single nucleus RNA-sequencing (snRNA-seq) to a model of murine DKD and five treatment regimens. We profiled a total of 70 mice from 14 groups, with N=4-6 mice per group.