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Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells
Mutations in the NPHS1 gene, which encodes NEPHRIN, cause congenital nephrotic syndrome, resulting from impaired slit diaphragm (SD) formation in glomerular podocytes. We previously reported NEPHRIN and SD abnormalities in the podocytes of kidney organoids generated from patient-derived induced plur...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890052/ https://www.ncbi.nlm.nih.gov/pubmed/33597637 http://dx.doi.org/10.1038/s41598-021-83501-9 |
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author | Ohmori, Tomoko De, Shankhajit Tanigawa, Shunsuke Miike, Koichiro Islam, Mazharul Soga, Minami Era, Takumi Shiona, Shinichi Nakanishi, Koichi Nakazato, Hitoshi Nishinakamura, Ryuichi |
author_facet | Ohmori, Tomoko De, Shankhajit Tanigawa, Shunsuke Miike, Koichiro Islam, Mazharul Soga, Minami Era, Takumi Shiona, Shinichi Nakanishi, Koichi Nakazato, Hitoshi Nishinakamura, Ryuichi |
author_sort | Ohmori, Tomoko |
collection | PubMed |
description | Mutations in the NPHS1 gene, which encodes NEPHRIN, cause congenital nephrotic syndrome, resulting from impaired slit diaphragm (SD) formation in glomerular podocytes. We previously reported NEPHRIN and SD abnormalities in the podocytes of kidney organoids generated from patient-derived induced pluripotent stem cells (iPSCs) with an NPHS1 missense mutation (E725D). However, the mechanisms underlying the disease may vary depending on the mutations involved, and thus generation of iPSCs from multiple patients is warranted. Here we established iPSCs from two additional patients with different NPHS1 mutations and examined the podocyte abnormalities in kidney organoids derived from these cells. One patient had truncating mutations, and NEPHRIN was undetectable in the resulting organoids. The other patient had a missense mutation (R460Q), and the mutant NEPHRIN in the organoids failed to accumulate on the podocyte surface to form SD precursors. However, the same mutant protein behaved normally when overexpressed in heterologous cells, suggesting that NEPHRIN localization is cell context-dependent. The localization of another SD-associated protein, PODOCIN, was impaired in both types of mutant organoids in a cell domain-specific manner. Thus, the new iPSC lines and resultant kidney organoids will be useful resources for dissecting the disease mechanisms, as well as for drug development for therapies. |
format | Online Article Text |
id | pubmed-7890052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78900522021-02-22 Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells Ohmori, Tomoko De, Shankhajit Tanigawa, Shunsuke Miike, Koichiro Islam, Mazharul Soga, Minami Era, Takumi Shiona, Shinichi Nakanishi, Koichi Nakazato, Hitoshi Nishinakamura, Ryuichi Sci Rep Article Mutations in the NPHS1 gene, which encodes NEPHRIN, cause congenital nephrotic syndrome, resulting from impaired slit diaphragm (SD) formation in glomerular podocytes. We previously reported NEPHRIN and SD abnormalities in the podocytes of kidney organoids generated from patient-derived induced pluripotent stem cells (iPSCs) with an NPHS1 missense mutation (E725D). However, the mechanisms underlying the disease may vary depending on the mutations involved, and thus generation of iPSCs from multiple patients is warranted. Here we established iPSCs from two additional patients with different NPHS1 mutations and examined the podocyte abnormalities in kidney organoids derived from these cells. One patient had truncating mutations, and NEPHRIN was undetectable in the resulting organoids. The other patient had a missense mutation (R460Q), and the mutant NEPHRIN in the organoids failed to accumulate on the podocyte surface to form SD precursors. However, the same mutant protein behaved normally when overexpressed in heterologous cells, suggesting that NEPHRIN localization is cell context-dependent. The localization of another SD-associated protein, PODOCIN, was impaired in both types of mutant organoids in a cell domain-specific manner. Thus, the new iPSC lines and resultant kidney organoids will be useful resources for dissecting the disease mechanisms, as well as for drug development for therapies. Nature Publishing Group UK 2021-02-17 /pmc/articles/PMC7890052/ /pubmed/33597637 http://dx.doi.org/10.1038/s41598-021-83501-9 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ohmori, Tomoko De, Shankhajit Tanigawa, Shunsuke Miike, Koichiro Islam, Mazharul Soga, Minami Era, Takumi Shiona, Shinichi Nakanishi, Koichi Nakazato, Hitoshi Nishinakamura, Ryuichi Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells |
title | Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells |
title_full | Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells |
title_fullStr | Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells |
title_full_unstemmed | Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells |
title_short | Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells |
title_sort | impaired nephrin localization in kidney organoids derived from nephrotic patient ips cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890052/ https://www.ncbi.nlm.nih.gov/pubmed/33597637 http://dx.doi.org/10.1038/s41598-021-83501-9 |
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