Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiation
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 une...
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doaj-3d81175a461c48f09c20182d5d09d5fd2020-11-25T01:04:47ZengBMCStem Cell Research & Therapy1757-65122017-09-018111710.1186/s13287-017-0645-8Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiationJiahui Huang0Shumin Zhou1Xin Niu2Bin Hu3Qing Li4Feng Zhang5Xue Zhang6Xiujuan Cai7Yuanlei Lou8Fen Liu9Chenming Xu10Yang Wang11Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan UniversityState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan UniversityKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesInstitute of Urology First Affiliated Hospital of Nanchang UniversityInstitute of Urology First Affiliated Hospital of Nanchang UniversityInstitute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong, University School of MedicineInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalAbstract 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.http://link.springer.com/article/10.1186/s13287-017-0645-8Induced pluripotent stem cellsAutosomal-dominant polycystic kidney diseaseDifferentiationKidney cellsSAMSN1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiahui Huang Shumin Zhou Xin Niu Bin Hu Qing Li Feng Zhang Xue Zhang Xiujuan Cai Yuanlei Lou Fen Liu Chenming Xu Yang Wang |
spellingShingle |
Jiahui Huang Shumin Zhou Xin Niu Bin Hu Qing Li Feng Zhang Xue Zhang Xiujuan Cai Yuanlei Lou Fen Liu Chenming Xu Yang Wang Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiation Stem Cell Research & Therapy Induced pluripotent stem cells Autosomal-dominant polycystic kidney disease Differentiation Kidney cells SAMSN1 |
author_facet |
Jiahui Huang Shumin Zhou Xin Niu Bin Hu Qing Li Feng Zhang Xue Zhang Xiujuan Cai Yuanlei Lou Fen Liu Chenming Xu Yang Wang |
author_sort |
Jiahui Huang |
title |
Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiation |
title_short |
Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiation |
title_full |
Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiation |
title_fullStr |
Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiation |
title_full_unstemmed |
Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiation |
title_sort |
generation of special autosomal dominant polycystic kidney disease ipscs with the capability of functional kidney-like cell differentiation |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2017-09-01 |
description |
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. |
topic |
Induced pluripotent stem cells Autosomal-dominant polycystic kidney disease Differentiation Kidney cells SAMSN1 |
url |
http://link.springer.com/article/10.1186/s13287-017-0645-8 |
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