Generation of patterned kidney organoids that recapitulate the adult kidney collecting duct system from expandable ureteric bud progenitors

Zipeng Zeng, Biao Huang, Riana K. Parvez, Yidan Li, Jyunhao Chen, Ariel C. Vonk, Matthew E. Thornton, Tadrushi Patel, Elisabeth A. Rutledge, Albert D. Kim, Jingying Yu, Brendan H. Grubbs, Jill A. McMahon, Nuria M. Pastor-Soler, Kenneth R. Hallows, Andrew P. McMahon and Zhongwei Li ()
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Zipeng Zeng: University of Southern California
Biao Huang: University of Southern California
Riana K. Parvez: University of Southern California
Yidan Li: University of Southern California
Jyunhao Chen: University of Southern California
Ariel C. Vonk: University of Southern California
Matthew E. Thornton: University of Southern California
Tadrushi Patel: University of Southern California
Elisabeth A. Rutledge: University of Southern California
Albert D. Kim: University of Southern California
Jingying Yu: University of Southern California
Brendan H. Grubbs: University of Southern California
Jill A. McMahon: University of Southern California
Nuria M. Pastor-Soler: University of Southern California
Kenneth R. Hallows: University of Southern California
Andrew P. McMahon: University of Southern California
Zhongwei Li: University of Southern California

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Current 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 human pluripotent stem cells. In chemically-defined culture conditions, UB organoids generate CD organoids, with differentiated principal and intercalated cells adopting spatial assemblies reflective of the adult kidney’s 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. Applying an efficient gene editing strategy to remove RET activity, we demonstrate genetically modified UB organoids can model congenital anomalies of kidney and urinary tract. Taken together, these platforms will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting duct system.

Date: 2021
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DOI: 10.1038/s41467-021-23911-5

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