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Generation of human-PSC derived kidney organoids with patterned nephron segments and a de novo vascular network
- Source :
- Cell Stem Cell
- Publication Year :
- 2019
-
Abstract
- Summary Human pluripotent stem cell-derived kidney organoids recapitulate developmental processes and tissue architecture, but intrinsic limitations, such as lack of vasculature and functionality, have greatly hampered their application. Here we establish a versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, producing a correlative level of vascular endothelial growth factor A (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 (ARPKD), 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.
- Subjects :
- Pluripotent Stem Cells
Vascular Endothelial Growth Factor A
Organogenesis
Neovascularization, Physiologic
Nephron
Biology
Kidney
Article
03 medical and health sciences
0302 clinical medicine
Organ Culture Techniques
Drug Discovery
Genetics
medicine
Organoid
Polycystic kidney disease
Humans
Progenitor cell
Precision Medicine
Induced pluripotent stem cell
Wnt Signaling Pathway
Cells, Cultured
030304 developmental biology
Polycystic Kidney, Autosomal Recessive
0303 health sciences
urogenital system
Wnt signaling pathway
Cell Differentiation
Cell Biology
Genetic Therapy
medicine.disease
Cell biology
Organoids
Vascular endothelial growth factor A
medicine.anatomical_structure
Molecular Medicine
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Stem Cell
- Accession number :
- edsair.doi.dedup.....74f821560395e2b81ccb73fe36d96f5b