A novel ADPKD model using kidney organoids derived from disease-specific human iPSCs

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder which manifests progressive renal cyst formation and leads to end-stage kidney disease. Around 85% of cases are caused by PKD1 heterozygous mutations, exhibiting relatively poorer renal outcomes than those with mutations i...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2020-09, Vol.529 (4), p.1186-1194
Main Authors: Shimizu, Tatsuya, Mae, Shin-Ichi, Araoka, Toshikazu, Okita, Keisuke, Hotta, Akitsu, Yamagata, Kunihiro, Osafune, Kenji
Format: Article
Language:English
Subjects:
ADPKD
Amino Acid Sequence
Base Sequence
Cell Differentiation - drug effects
Cell Line
Colforsin - pharmacology
Disease model
Drug Evaluation, Preclinical
Humans
Induced Pluripotent Stem Cells - drug effects
Induced Pluripotent Stem Cells - pathology
Kidney - pathology
Kidney organoid
Models, Biological
Mutation - genetics
Organoids - pathology
Patient-derived hiPSC
Phenotype
PKD1 gene-edited hiPSC
Polycystic Kidney, Autosomal Dominant - pathology
TRPP Cation Channels - chemistry
TRPP Cation Channels - genetics
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Summary:Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder which manifests progressive renal cyst formation and leads to end-stage kidney disease. Around 85% of cases are caused by PKD1 heterozygous mutations, exhibiting relatively poorer renal outcomes than those with mutations in other causative gene PKD2. Although many disease models have been proposed for ADPKD, the pre-symptomatic pathology of the human disease remains unknown. To unveil the mechanisms of early cytogenesis, robust and genetically relevant human models are needed. Here, we report a novel ADPKD model using kidney organoids derived from disease-specific human induced pluripotent stem cells (hiPSCs). Importantly, we found that kidney organoids differentiated from gene-edited heterozygous PKD1-mutant as well as ADPKD patient-derived hiPSCs can reproduce renal cysts. Further, we demonstrated the possibility of ADPKD kidney organoids serving as drug screening platforms. This newly developed model will contribute to identifying novel therapeutic targets, extending the field of ADPKD research. •A novel model for ADPKD is established using kidney organoids derived from hiPSCs.•PKD1 gene-edited and patient-derived kidney organoids can reproduce cystogenesis.•ADPKD kidney organoids provide a novel platform for identifying candidate drugs.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.06.141