[PDF][PDF] Plasticity of distal nephron epithelia from human kidney organoids enables the induction of ureteric tip and stalk

SE Howden, SB Wilson, E Groenewegen, L Starks… - Cell Stem Cell, 2021 - cell.com
SE Howden, SB Wilson, E Groenewegen, L Starks, TA Forbes, KS Tan, JM Vanslambrouck
Cell Stem Cell, 2021cell.com
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 …
Summary
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.
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