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- Title
Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types.
- Authors
Shi, Min; McCracken, Kyle W.; Patel, Ankit B.; Zhang, Weitao; Ester, Lioba; Valerius, M. Todd; Bonventre, Joseph V.
- Abstract
Directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia is essential to kidney regenerative medicine. Here we describe highly efficient, serum-free differentiation of hPSCs into ureteric bud (UB) organoids and functional CD cells. The hPSCs are first induced into pronephric progenitor cells at 90% efficiency and then aggregated into spheres with a molecular signature similar to the nephric duct. In a three-dimensional matrix, the spheres form UB organoids that exhibit branching morphogenesis similar to the fetal UB and correct distal tip localization of RET expression. Organoid-derived cells incorporate into the UB tips of the progenitor niche in chimeric fetal kidney explant culture. At later stages, the UB organoids differentiate into CD organoids, which contain >95% CD cell types as estimated by single-cell RNA sequencing. The CD epithelia demonstrate renal electrophysiologic functions, with ENaC-mediated vectorial sodium transport by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells. Kidney collecting duct cells with physiologic functions are generated from human pluripotent stem cells.
- Publication
Nature Biotechnology, 2023, Vol 41, Issue 2, p252
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/s41587-022-01429-5