Journal Article

DKFZ-2022-01697

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cystic renal-epithelial derived induced pluripotent stem cells from polycystic kidney disease patients

Kenter, A. T. ; Rentmeester, E. ; van Riet, J.Extern* ; Boers, R. ; Boers, J. ; Ghazvini, M. ; Xavier, V. J. ; Leenders, G. J. L. H. ; Verhagen, P. C. M. S. ; Til, M. E. ; Eussen, B. ; Losekoot, M. ; Klein, A. ; Peters, D. J. M. ; IJcken, W. F. J. ; Werken, H. J. G. ; Zietse, R. ; Hoorn, E. J. ; Jansen, G. ; Gribnau, J. H.

2020
AlphaMed Press Durham

This record in other databases:

Please use a persistent id in citations: doi:10.1002/sctm.18-0283

Abstract: Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to kidney failure in most patients. In approximately 85% of cases, the disease is caused by mutations in PKD1. How dysregulation of PKD1 leads to cyst formation on a molecular level is unknown. Induced pluripotent stem cells (iPSCs) are a powerful tool for in vitro modeling of genetic disorders. Here, we established ADPKD patient-specific iPSCs to study the function of PKD1 in kidney development and cyst formation in vitro. Somatic mutations are proposed to be the initiating event of cyst formation, and therefore, iPSCs were derived from cystic renal epithelial cells rather than fibroblasts. Mutation analysis of the ADPKD iPSCs revealed germline mutations in PKD1 but no additional somatic mutations in PKD1/PKD2. Although several somatic mutations in other genes implicated in ADPKD were identified in cystic renal epithelial cells, only few of these mutations were present in iPSCs, indicating a heterogeneous mutational landscape, and possibly in vitro cell selection before and during the reprogramming process. Whole-genome DNA methylation analysis indicated that iPSCs derived from renal epithelial cells maintain a kidney-specific DNA methylation memory. In addition, comparison of PKD1+/− and control iPSCs revealed differences in DNA methylation associated with the disease history. In conclusion, we generated and characterized iPSCs derived from cystic and healthy control renal epithelial cells, which can be used for in vitro modeling of kidney development in general and cystogenesis in particular.

---

---

Database coverage:
; ; ; Article Processing Charges ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---