Generation of Human PSC-Derived Kidney Organoids with Patterned Nephron Segments and a De Novo Vascular Network

Published: 12 July 2019| Version 5 | DOI: 10.17632/mxpdwxgjy5.5
Contributors:
Jian Hui Low,
Pin Li,
Elaine Chew,
Bingrui Zhou,
Tian Zhang,
Michelle Lian,
Meng Liu,
Jia Nee Foo,
Juan Carlos Izpisua Belmonte,
Yun Xia

Description

Human pluripotent stem cells-derived kidney organoids recapitulate developmental processes and tissue architectures, but intrinsic limitations, such as a lack of vasculature and functionality, have greatly hampered their application. Here we establish a versatile protocol for generating vascularized three-dimensional kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, thereby producing a correlative level of VEGFA to define a resident vascular network. Single cell RNA-sequencing identifies a subset of nephron progenitor cells as a potential source of renal vasculature. These kidney organoids undergo further structural and functional maturation upon implantation. Using this kidney organoid platform, we establish an in vitro model of autosomal recessive polycystic kidney disease, the cystic phenotype of which can be effectively prevented by gene correction or drug treatment. Our studies provide new avenues for studying human kidney development, modeling disease pathogenesis, and performing patient-specific drug validation.

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Institutions

Lee Kong Chian School of Medicine

Categories

Pluripotent Stem Cell Differentiation

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