来自iPSC的人类β类细胞和SLC30A8疾病模型的电生理学表征
Manon Jaffredo1, Nicole A J Krentz2,3, Benoite Champon2,4
1University of Bordeaux, CNRS, Institute of Chemistry and Biology of Membranes and Nano-objects, UMR 5248, Pessac, France.
bioRxiv : the preprint server for biology
|October 31, 2023
概括
诱导多能干细胞衍生的人类β类细胞 (BLC) 对治疗和疾病建模具有前景. 电生理学工具有效评估BLC功能,揭示了对电气合和遗传变异影响的见解.
科学领域:
- 细胞生物学 细胞生物学
- 电子生理学 电子生理学
- 糖尿病研究研究 糖尿病研究
背景情况:
- 诱导多能干细胞衍生的人类β类细胞 (BLC) 为细胞疗法和疾病建模提供了潜力.
- 目前对BLC的功能评估是有限的,主要集中在转录学和形态学上.
研究的目的:
- 验证用于评估BLC功能的电生理学工具.
- 描述BLC的电特性和胰岛素分泌机制.
- 评估遗传变异对BLC功能的影响.
主要方法:
- 多细胞和单细胞电生理学使用多电极阵列 (MEAs) 和补丁.
- 测量细胞外电活动,慢电位 (SP) 信号和细胞外特性.
- 电压离子电流 (,,KATP) 和电气合的表征.
主要成果:
- BLCs表现出电气合,并产生与胰岛素分泌相关的SP信号,类似于初级β细胞.
- 单细胞补丁显示了与初级β细胞和EndoC-βH1细胞相似的电压受控电流.
- 在BLC中较大的KATP通道导电性可能解释了降低的葡萄糖响应.
- MEAs表明,具有SLC30A8保护性等位基因的BLCs显示了增强的电气合.
结论:
- 电生理学方法被验证用于功能BLC评估.
- 具有2型糖尿病保护性*SLC30A8*等位基因的BLCs显示了增强的电气合.
- 适应的电生理学方法可以评估基因变异对BLC功能和合的影响.
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