APOL1风险变异诱导患者衍生脏器官中细胞的代谢重编程
Heein Song1, Sébastien J Dumas2, Gangqi Wang2
1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands.
Stem cell reports
|October 3, 2025
概括
具有两个阿波利波蛋白L1 (APOL1) 基因风险变异 (RVs) 的个体面临更高的慢性病风险. 这项研究表明,炎症性损伤引发了线粒体功能障碍和RV podocytes中的代谢重编程,这是早期疾病的关键.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 患有两个阿波利波蛋白L1 (APOL1) 基因风险变异 (RVs) 的人患慢性病 (CKD) 的风险增加.
- APOL1介导病 (AMKD) 的发病因子,特别是早期的细胞变化,仍然不完全理解.
研究的目的:
- 在脏器官中使用患者衍生的诱导多能干细胞 (iPSC) 建模AMKD.
- 研究携带APOL1RVs的受体细胞对炎症刺激的早期细胞和代谢反应.
主要方法:
- 从APOL1 G1/G2 RVs同卵性患者的iPSC中生成脏器官.
- 单细胞转录组学,免疫光成像和空间动态代谢组学.
- 在隔离的血球细胞和iPSC衍生的受体细胞中评估线粒体功能.
主要成果:
- 在RV podocytes中APOL1上调和炎症信号传递 (干扰素-马).
- 显著减少氧化酸化和TCA循环活性,增加RV podocytes中的糖解和缺氧信号.
- 在炎症挑战后,iPSC衍生的RV podocytes中的线粒体呼吸功能受损和线粒体分支减少.
结论:
- 炎症性损伤诱导APOL1RV podocytes中的早期代谢重编程.
- 线粒体功能障碍是AMKD病理生理学的早期阶段的一个关键因素.
- 开发的器官模型有效地回顾了AMKD的关键方面,为进一步研究提供了一个平台.
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