Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types

Shi, Min, McCracken, Kyle W., Patel, Ankit B., Zhang, Weitao, Ester, Lioba, Valerius, M. Todd ORCID: 0000-0001-8143-9231 and Bonventre, Joseph, V . Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types. Nat. Biotechnol.. BERLIN: NATURE PORTFOLIO. ISSN 1546-1696

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DOI:10.1038/s41587-022-01429-5

Abstract

Kidney collecting duct cells with physiologic functions are generated from human pluripotent stem cells. 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.

Item Type:

Journal Article

Creators:

Creators	Email	ORCID	ORCID Put Code
Shi, Min	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
McCracken, Kyle W.	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Patel, Ankit B.	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Zhang, Weitao	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Ester, Lioba	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Valerius, M. Todd	UNSPECIFIED	orcid.org/0000-0001-8143-9231	UNSPECIFIED
Bonventre, Joseph, V	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED