Generation of kidney ureteric bud and collecting duct organoids that recapitulate kidney branching morphogenesis

Zeng, Zipeng; Huang, Biao; Parvez, Riana K.; Li, Yidan; Chen, Jyunhao; Vonk, Ariel; Thornton, Matthew E.; Patel, Tadrushi; Rutledge, Elisabeth A.; Kim, Albert D.; Yu, Jingying; Pastor-Soler, Nuria; Hallows, Kenneth R.; Grubbs, Brendan H.; McMahon, Jill A.; McMahon, Andrew P.; Li, Zhongwei

Kidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney’s collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or generated de novo from pluripotent human stem cells. UB organoids differentiate into CD organoids in vitro, with differentiated cell types adopting spatial assemblies reflective of the adult kidney collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids in vitro results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Combining efficient gene editing with the UB organoid model will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting system. One sentence summary Collecting duct organoids derived from primary mouse and human ureteric bud progenitor cells and human pluripotent stem cells provide an in vitro platform for genetic dissection of development, regeneration and diseases of the mammalian collecting system.