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| Status |
Public on May 29, 2019 |
| Title |
Generating Patterned Kidney Organoids for Studying Development and Diseases [bulk RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Human pluripotent stem cells (hPSCs)-derived kidney organoids recapitulate complex developmental processes and tissue architectures, but the intrinsic limitations, such as variability and a lack of vasculature, have greatly hampered their application. Here we establish a highly efficient and 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, thereby producing a correlative level of VEGFA to define the resident vascular network. By single cell RNA-sequencing, we identify a subset of nephron progenitor cells as a potential source of the vasculature. Upon implantation into host mice, these kidney organoids undergo further structural and functional maturation, as demonstrated by the size-selective handling of dextran. Based on this differentiation platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD) by differentiating induced PSCs (iPSCs) from an ARPKD patient into 3D kidney organoids that develop tubule cysts in response to cAMP upregulation. The cystogenesis phenotype can be effectively prevented by gene correction or drug treatment. Our studies provide a versatile platform for studying human kidney development and diseases, and opens new avenues for modeling disease pathogenesis and performing patient-specific drug screening.
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| Overall design |
Examination of transcriptome in human pluripotent stem cells-derived vascularized three-dimensional kidney organoids. Day 0 organoid (technical duplicate), Day 10 organoid (technical duplicate), Day 24 organoid (technical duplicate), 2-week implanted organoid (technical triplicate), 4-week implanted organoid (technical triplicate).
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| Contributor(s) |
Xia Y |
| Citation(s) |
31303547 |
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| Submission date |
May 28, 2019 |
| Last update date |
Aug 28, 2019 |
| Contact name |
M.P. Philipott |
| Organization name |
Blizard Institute Barts and The London School of Medicine and Dentistry
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| Department |
Center for Molecular Medicine Cologne
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| Street address |
4 Newark St
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| City |
London |
| ZIP/Postal code |
E1 2AT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE132026 |
Generating Patterned Kidney Organoids for Studying Development and Diseases |
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| Relations |
| BioProject |
PRJNA545106 |
| SRA |
SRP199644 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE131841_Day0_Day10_Day24_invivo2weeks_invivo4weeks.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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