Identification of renal cyst cells of type I Nephronophthisis by single-nucleus RNA sequencing

Type I nephronophthisis, the most common form of nephronophthisis, generally results from gene deletions of NPHP1, and cyst formation at the corticomedullary junction is one of its most dominant pathological features. The isolation and identification of cyst cell subpopulations would greatly promote the elucidation of the mechanism of renal cystogenesis in nephronophthisis. In this study, we have successfully mapped a comprehensive atlas of renal cellular landscape by single-nucleus RNA sequencing of NPHP1 mice as well as identified a specific group of renal cyst cells. A molecular marker of cyst cells, Fam129a, was found to be localized in the renal cyst cytoplasm of NPHP1 mice and patients. In addition, both the proliferation and apoptotic activity of NPHP1 cyst cells were enhanced. This work offers a valuable resource for further exploring the molecular mechanism of NPHP1 renal cystogenesis and for the treatment of this disease.