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HUMAN FETAL KIDNEY ORGANOIDS MODEL EARLY NEPHROGENESIS AND NOTCH-DRIVEN CELL FATE [scRNA-Seq 2]

ABSTRACT: Pluripotent stem cell–derived kidney organoids (PSC-KOs) are widely used to model human kidney development and disease. However, organoids from human fetal kidney tissue (hFKOs), which could benchmark PSC-KOs, remain underdeveloped. Here, using a chemically defined serum-free medium, we established a prolonged culture protocol for hFKOs that self-organize into polarized renal epithelium, reinitiate from NCAM1+ progenitors, and recapitulate nephrogenic and ureteric bud lineages. Bulk transcriptomics, single-cell RNA sequencing, pseudotime analysis, and immunostaining revealed diverse cell populations, with a preserved epithelial progenitor pool and tubular differentiation axis—both more robust than in PSC-KOs. hFKOs were enriched for NOTCH signaling genes, enabling single-cell analysis of pharmacological NOTCH inhibition. This revealed a maturation block with increased nephron progenitors and a bias toward distal over early proximal tubule fates. We also identified a novel prominin-1–expressing cell state that evades NOTCH inhibition to generate both proximal and distal tubules. Overall, hFKOs provide a developmentally faithful model and offer critical insights into kidney morphogenesis, advancing the fields of stem cell biology and regenerative medicine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE300309 | GEO | 2025/09/10

REPOSITORIES: GEO

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