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

作者：Zipeng Zeng, Biao Huang, Riana K. Parvez, Yidan Li, Jy-Pyn Chen, Ariel C Vonk, M. Thornton, Tadrushi Patel, Elisabeth A. Rutledge, Albert D. Kim, Jingying Yu, B. Grubbs, J. McMahon, N. Pastor-Soler, K. Hallows, A. McMahon, Zhongwei Li · 发表于：Nature Communications · 年份：2021 · DOI：10.1038/s41467-021-23911-5 · 被引用次数：109 · 研究领域：Medicine

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. Here, the authors model the collecting duct system in kidneys by taking ureteric bud (UB) progenitor cells from both mouse and human primary tissues, as well as from hESC and hiPSC to generate organoids, which can model congenital anomalies of the kidney and urinary tract.