Gene expression profile at bulk (24h, 48h & 72h) and single nucleus (24h) level of mouse right kidney post sham operation and unilateral nephrectomy.

The mechanism driving the remarkable ability of the remaining kidney to enlarge and increase its function following removal of its contralateral pair remains elusive. To explore the pathways driving compensatory renal hypertrophy, comprehensive RNA-seq transcriptional studies in the kidneys of mice undergoing hypertrophy 24, 48 and 72 hours following nephrectomy have been undertaken and compared with mice undergoing sham operations. The results reveal substantial time dependent enhancement of cholesterol biosynthesis pathways, increases in mitochondrial gene expression and cell cycle perturbations. Single nuclei RNA-Seq 24 hours post nephrectomy was used to further explore cholesterol biosynthesis signature and its driver SREBP2. In a cell specific manner, snRNA-seq demonstrated that SREBP2 activity increases in proximal tubules and medullary thick ascending limb and is responsible for cell size regulation following IGF-1 stimulation. These results suggest a previously undescribed role for SREBP2 in the mechanism underlying compensatory renal hypertrophy. This mechanism might be amenable to therapeutic manipulation to enhance kidney size and function.