Organoid-based analysis of human kidney development and disease

Abstract

Recapitulating the three-dimensional organ structure in vitro is a major challenge for developmental biology and regenerative medicine. The kidney develops by the reciprocal interactions between the nephron progenitor and ureteric bud, and the origins of these two types of precursors are spatially distinct. Based on these developmental findings, we previously established the induction protocols of the nephron progenitors from pluripotent stem cells (PSCs). Induced nephron progenitors robustly formed nephrons: glomeruli and renal tubules. By generating iPS cellderived nephron organoids from a patient with the congenital nephrotic syndrome, we reproduced the glomerular abnormalities that represent the initial phase of this disease. We also established the protocols to induce the ureteric bud from mouse and human PSCs. Mouse organoids reassembled from the differentially induced ureteric bud and nephron progenitors developed the inherent architectures of the embryonic kidney. Humans ureteric bud organoids were applied to autosomal dominant polycystic kidney disease to successfully reproduce cyst formation in vitro. Thus, kidney organoids will serve as useful basis to analyze human kidney development and disease.