Single-cell RNA sequencing-based identification of novel podocyte injury-associated genes from isolated glomeruli of diabetic db/db mice [RNA-seq]

Because podocytes are underrepresented in whole-kidney single-cell RNA sequencing datasets, we performed single-cell RNA sequencing of isolated glomeruli from diabetic db/db mice and control db/m mice to generate a glomerulus-focused transcriptomic dataset. Diabetic glomeruli showed reduced podocyte abundance and extensive transcriptional remodeling.

Integration of this in vivo dataset with in vitro analyses of cultured human podocytes exposed to diabetic stimuli identified OPCML, ADM, NELL2, and DHRS3 as candidate genes associated with diabetic podocyte injury. These findings identify OPCML, ADM, and DHRS3 as novel mediators of podocyte injury and potential therapeutic targets for DKD.