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GRP94对于人类诱导多能干细胞的最终内皮规范是不可或缺的

Hua Wei¹, Christiana Kappler², Erica Green¹

¹Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.

Molecular therapy : the journal of the American Society of Gene Therapy

|April 21, 2025

概括

葡萄糖调节蛋白94 (GRP94) 对于人类干细胞分化为产生胰岛素的β细胞至关重要. GRP94减轻了内等质网膜压力,并支持WNT信号传输,这对于糖尿病细胞治疗的发展至关重要.

科学领域:

干细胞生物学干细胞生物学
内分泌学在内分泌学.
分子生物学分子生物学

背景情况:

人类诱导多能干细胞 (hiPSC) 衍生β细胞疗法为糖尿病治疗提供了潜在的潜力.
优化hiPSC差异化需要了解遗传调节者.
葡萄糖调节蛋白94 (GRP94) 在人类β细胞发育中的作用尚未被探索.

研究的目的:

研究 GRP94 在 hiPSCs 的人类β细胞发育中的作用.
确定GRP94对最终内皮 (DE) 形成和β细胞分化的影响.
阐明GRP94在减轻压力和调节信号通路方面的机制.

主要方法:

生成的HSP90B1/GRP94淘汰赛 (KO) 的hiPSCs.
在KO hiPSCs中重新表达的GRP94.
诱导β细胞分化并分析DE形成,细胞死亡和WNT/β-catenin信号传递.

主要成果:

GRP94的耗尽显著阻碍了β细胞的产生.
在DE分化过程中,GRP94缺乏会通过内质网膜 (ER) 应激增加细胞死亡.
删除GRP94降低了WNT/β-catenin信号激活,这对于DE规范至关重要.

结论:

GRP94对于人类的DE形成和随后的hiPSCs的β细胞发育是不可或缺的.
GRP94减轻了ER压力诱导的细胞死亡,并调节了WNT/β-catenin信号传递.
准GRP94通路可能会增强糖尿病的hiPSC衍生细胞疗法.

关键词:

压力ERER压力ERER压力人类诱导的多能干细胞干细胞.在WNT/β-catenin信号传输中.细胞死亡调节细胞死亡调节最终的内皮发展.葡萄糖调节蛋白质 94 调节葡萄糖的蛋白质这就是hiPSCs.产生胰岛素的细胞.基于干细胞的糖尿病治疗方法 1型糖尿病治疗治疗方法 β细胞分化 β细胞分化

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