APOL1 risk variants induce metabolic reprogramming of podocytes in patient-derived kidney organoids.

ABSTRACT: Carriers of two apolipoprotein L1 gene risk variants (RVs), termed G1 and G2, are at increased risk for chronic kidney disease. This study utilized induced pluripotent stem cells (iPSCs) derived from two patients homozygous for G1 and G2 to model human apolipoprotein L1 (APOL1)-mediated kidney disease (AMKD) in kidney organoids. Single-cell transcriptomic analysis and immunofluorescence imaging showed APOL1 upregulation in podocytes after interferon-gamma (IFN-γ) treatment. Transcriptomics and spatial dynamic metabolomics demonstrated a significant reduction in oxidative phosphorylation and tricarboxylic acid (TCA) cycle activity, along with upregulation of glycolysis and hypoxia signaling in RV podocytes. Isolated RV glomeruli exhibited no increase in maximal respiration rate following IF

SUBMITTER: Song H 

PROVIDER: S-EPMC12790724 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature