Developmental Hypoxia Enhances Kidney Organoid Complexity and Maturity.

ABSTRACT: Reciprocal signaling between metanephric mesenchyme (MM) and ureteric bud (UB) is essential for human kidney development. However, human pluripotent stem cell-derived kidney organoids do not incorporate UB differentiation, limiting organoid maturation and disease modeling. Here, a hypoxia-based differentiation method inspired by developmental cues is reported that produces mature kidney organoids with collecting duct-like tubules connected to multiple nephrons. Hypoxia promotes the co-induction of MM and UB-like progenitors within the same culture dish. The augmented expression of reciprocal signaling genes guides the differentiation of the kidney organoids into highly structured tubular networks, mature RNA profiles, and a more realistic micro-anatomy, leading to higher-order kidney organ

SUBMITTER: Lim H 

PROVIDER: S-EPMC12561403 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature