Generation of Special Autosomal Dominant Polycystic Kidney Disease IPSCs with the Capability of Functional Kidney-like Cell Differentiation

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2017 Sep 21

PMID 28927462

Citations 2

Authors

Jiahui Huang

Shumin Zhou

Xin Niu

Bin Hu

Qing Li

Feng Zhang

Xue Zhang

Xiujuan Cai

Yuanlei Lou

Fen Liu

Chenming Xu

Yang Wang

Affiliations

Soon will be listed here.

Abstract

Background: Human induced pluripotent stem cells (iPSCs) have been verified as a powerful cell model for the study of pathogenesis in hereditary disease. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of PKD or non-PKD genes. The pathogenesis of ADPKD remains unexplored because of the lack of a true human cell model.

Methods: Six ADPKD patients and four healthy individuals were recruited as donors of somatic cells from a Chinese ADPKD family without mutations of the PKD genes but carrying SAMSN1 gene deletion. The ADPKD-iPSCs were generated from somatic cells and were induced into kidney-like cells (KLCs) by a novel three-step method involving cytokines and renal epithelium growth medium. Furthermore, we analyzed functional properties of these KLCs by water transportation and albumin absorption assays.

Results: We successfully generated iPSCs from ADPKD patients and differentiated them into KLCs that showed morphological and functional characteristics of human kidney cells. Further, we also found that ADPKD-iPSC-KLCs had a significantly higher rate of apoptosis and a significantly lower capacity for water transportation and albumin absorption compared to healthy sibling-derived differentiated KLCs. Furthermore, knockdown of SAMSN1 in control iPSCs may attenuate differentiation and/or function of KLCs.

Conclusions: These data show that we have created the first iPSCs established from ADPKD patients without mutations in the PKD genes, and suggest that the deletion mutation of SAMSN1 might be involved in the differentiation and/or function of KLCs. ADPKD-iPSC-KLCs can be used as a versatile model system for the study of kidney disease.

Citing Articles

Lama2 And Samsn1 Mediate the Effects of Brn4 on Hippocampal Neural Stem Cell Proliferation and Differentiation.

Zhang L, Zhang X, Ji R, Ji Y, Wu Y, Ding X Stem Cells Int. 2023; 2023:7284986.

PMID: 37091532 PMC: 10118897. DOI: 10.1155/2023/7284986.

Fundamental insights into autosomal dominant polycystic kidney disease from human-based cell models.

Weydert C, Decuypere J, De Smedt H, Janssens P, Vennekens R, Mekahli D Pediatr Nephrol. 2018; 34(10):1697-1715.

PMID: 30215095 DOI: 10.1007/s00467-018-4057-5.

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