类有机物
包装D1
常染色体显性多囊肾病
诱导多能干细胞
生物
囊肿
维甲酸
细胞生物学
体外
多囊肾病
癌症研究
胚胎干细胞
肾
病理
医学
内分泌学
细胞培养
遗传学
基因
作者
Shin-Ichi Mae,Fumihiko Hattanda,Hiroyuki Morita,Aya Nozaki,Naoko Katagiri,Hideomi Ogawa,Kaori Teranaka,Y Nishimura,Aoi Kudoh,Sanae Yamanaka,Kyoko Matsuse,Makoto Ryosaka,Akira Watanabe,Tomoyoshi Soga,S. Nishio,Kenji Osafune
出处
期刊:Cell Reports
[Elsevier]
日期:2023-12-01
卷期号:42 (12): 113431-113431
被引量:1
标识
DOI:10.1016/j.celrep.2023.113431
摘要
In autosomal dominant polycystic kidney disease (ADPKD), renal cyst lesions predominantly arise from collecting ducts (CDs). However, relevant CD cyst models using human cells are lacking. Although previous reports have generated in vitro renal tubule cyst models from human induced pluripotent stem cells (hiPSCs), therapeutic drug candidates for ADPKD have not been identified. Here, by establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to CDs, we succeed in advancing the developmental stage of CD organoids and show that all CD organoids derived from PKD1−/− hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis. Moreover, we identify retinoic acid receptor (RAR) agonists as candidate drugs that suppress in vitro cystogenesis and confirm the therapeutic effects on an ADPKD mouse model in vivo. Therefore, our in vitro CD cyst model contributes to understanding disease mechanisms and drug discovery for ADPKD.
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