Details

Autor(en) / Beteiligte

• Shi, Min
• McCracken, Kyle W
• Patel, Ankit B
• Zhang, Weitao
• Ester, Lioba
• Valerius, M Todd
• Bonventre, Joseph V

Titel

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

Ist Teil von

• Nature biotechnology, 2023-02, Vol.41 (2), p.252-261

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Beschreibungen/Notizen

• 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.