Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types.
Nat Biotechnol
; 41(2): 252-261, 2023 02.
Article
in En
| MEDLINE
| ID: mdl-36038632
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ureter
/
Pluripotent Stem Cells
Limits:
Humans
Language:
En
Journal:
Nat Biotechnol
Year:
2023
Document type:
Article