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Partial nephrectomy is a surgical technique as an alternative for traditional radical nephrectomy. The advantage of partial nephrectomy technique is nephron-sparing, however, whether the remaining kidney tissue could regenerate the lost nephron is still unknown. The current work is to investigate the kidney tissue repair process and the related cellular and molecular mechanism.We used a novel unilateral partial nephrectomy mouse model to study kidney repair, and focused on a population of Sox9+ progenitor cells to study their pivotal role in the regenerative process. Kidney function after nephrectomy was measured using creatinine and urea nitrogen assay kit. Wound healing was assessed by Masson Trichrome Staining. Tissue regeneration was tested by Sox9+ cells immunofluorescence staining. The differentiation potential of Sox9+ cells were assessed by immunoanalysis with various tubular cell markers. Notch activation was determined by qPCR and Western blotting.After partial nephrectomy, we found that massive Sox9+ cells emerged one day after the surgery and lasted for up to 20 days. The Sox9+ cells had proliferative capacity and could give rise to epithelial cells of proximal tubule, Henle's loop, distal tubule, collecting duct, and the parietal layer of glomerulus. We also found that the activation of Sox9+ cells was mediated by Notch signaling pathway.The current study reveals that Notch-mediated Sox9+ cell activation can contribute to kidney tubule regeneration after unilateral partial nephrectomy in mice.