biostudies-literatureHowden SENIDDK NIH HHSNierstichtingNational Institutes of HealthChan Zuckerberg InitiativeNIGMS NIH HHSAustralian Research Council671-684.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC8026527biostudies-literatureUnknown28(4)During development, distinct progenitors contribute to the nephrons versus the ureteric epithelium of the kidney. Indeed, previous human pluripotent stem-cell-derived models of kidney tissue either contain nephrons or pattern specifically to the ureteric epithelium. By re-analyzing the transcriptional distinction between distal nephron and ureteric epithelium in human fetal kidney, we show here that, while existing nephron-containing kidney organoids contain distal nephron epithelium and no ureteric epithelium, this distal nephron segment alone displays significant in vitro plasticity and can adopt a ureteric epithelial tip identity when isolated and cultured in defined conditions. "Induced" ureteric epithelium cultures can be cryopreserved, serially passaged without loss of identity, and transitioned toward a collecting duct fate. Cultures harboring loss-of-function mutations in PKHD1 also recapitulate the cystic phenotype associated with autosomal recessive polycystic kidney disease.Cell stem cellPlasticity of distal nephron epithelia from human kidney organoids enables the induction of ureteric tip and stalk.PMC8026527T32 GM145304UH3 DK107344U01 DK107350Jain SGroenewegen ELittle MHStarks LTan KSHowden SEForbes TAChen YHHolloway EMWilson SBVanslambrouck JMSpence JRfalsePlasticity of distal nephron epithelia from human kidney organoids enables the induction of ureteric tip and stalk.During development, distinct progenitors contribute to the nephrons versus the ureteric epithelium of the kidney. Indeed, previous human pluripotent stem-cell-derived models of kidney tissue either contain nephrons or pattern specifically to the ureteric epithelium. By re-analyzing the transcriptional distinction between distal nephron and ureteric epithelium in human fetal kidney, we show here that, while existing nephron-containing kidney organoids contain distal nephron epithelium and no ureteric epithelium, this distal nephron segment alone displays significant in vitro plasticity and can adopt a ureteric epithelial tip identity when isolated and cultured in defined conditions. "Induced" ureteric epithelium cultures can be cryopreserved, serially passaged without loss of identity, and transitioned toward a collecting duct fate. Cultures harboring loss-of-function mutations in PKHD1 also recapitulate the cystic phenotype associated with autosomal recessive polycystic kidney disease.2021-01-01T00:00:00Z2021 Apr2026-05-02T22:39:53.603Z2025-04-05T09:58:39.583ZS-EPMC80265273337864710.1016/j.stem.2020.12.001