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Title :Organoids from Nephrotic Disease-Derived iPSCs Identify Impaired NEPHRIN Localization and Slit Diaphragm Formation in Kidney Podocytes
Authors :Tanigawa, Shunsuke
Islam, Mazharul
Sharmin, Sazia
Naganuma, Hidekazu
Yoshimura, Yasuhiro
Haque, Fahim
Era, Takumi
Nakazato, Hitoshi
Nakanishi, Koichi
Sakuma, Tetsushi
Yamamoto, Takashi
Kurihara, Hidetake
Taguchi, Atsuhiro
Nishinakamura, Ryuichi
Issue Date :11-Sep-2018
Abstract :Mutations in the NPHS1 gene, which encodes NEPHRIN, cause congenital nephrotic syndrome, resulting from impaired slit diaphragm (SD) formation in glomerular podocytes. However, methods for SD reconstitution have been unavailable, thereby limiting studies in the field. In the present study, we established human induced pluripotent stem cells (iPSCs) from a patient with an NPHS1 missense mutation, and reproduced the SD formation process using iPSC-derived kidney organoids. The mutant NEPHRIN failed to become localized on the cell surface for pre-SD domain formation in the induced podocytes. Upon transplantation, the mutant podocytes developed foot processes, but exhibited impaired SD formation. Genetic correction of the single amino acid mutation restored NEPHRIN localization and phosphorylation, colocalization of other SD-associated proteins, and SD formation. Thus, these kidney organoids from patient-derived iPSCs identified SD abnormalities in the podocytes at the initial phase of congenital nephrotic disease.
URL :https://doi.org/10.1016/j.stemcr.2018.08.003
Type Local :雑誌掲載論文
ISSN :2213-6711
Publisher :Cell Press
URI :http://hdl.handle.net/20.500.12000/46025
Citation :Stem Cell Reports Vol.11 no.3 p.727 -740
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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