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在多西环林可诱导控制下表达干扰素β的iPSCs的生成

Olga Sheveleva¹, Nina Butorina¹, Elena Protasova¹

¹Laboratory of Cellular and Molecular Basis of Histogenesis, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow 119334, Russia.

International journal of molecular sciences

|September 13, 2025

概括

研究人员开发了能够控制干扰素β (IFNB1) 生产的转基因人类诱导多能干细胞 (iPSC). 这种创新的细胞模型为研究IFNB1提供了一个新的途径.

科学领域:

干细胞生物学干细胞生物学
免疫学免疫学免疫学
基因编辑基因编辑

背景情况:

1型干扰素 (IFN-Is) 具有显著的抗病毒,抗瘤和免疫调节功能,表明其具有治疗潜力.
系统性给予IFN-Is可能会导致副作用,并且它们在特定病理状况中的作用仍然没有确定性.
通过基于细胞的疗法进行本地调节的IFN-I生产可以克服与系统管理相关的局限性.

研究的目的:

为了产生转基因人类诱导多能干细胞 (iPSCs),用于控制局部生产干扰素β (IFNB1).
建立一个细胞模型来研究IFNB1的生物和治疗作用.
为产生具有诱导IFNB1表达的多种细胞类型创建一个平台.

主要方法:

使用CRISPR/Cas9技术生成可诱导多西环素的IFNB1过度表达的iPSC线 (IFNB-iPSC) 和控制线 (TA-iPSC).
通过形态学,关键标记物的表达 (OCT4,SOX2,TRA 1-60,NANOG) 和分化潜力来确认生成的细胞系的多能性.
在多西环林诱导后IFNB-iPSC中验证了IFNB1基因和蛋白质上调.

主要成果:

成功生成了四个iPSC线:三个IFNB1过度表达 (IFNB-iPSC) 和一个控制 (TA-iPSC).
在所有生成的iPSC线条中确认了多能性和稳定的基因修饰.
在IFNB-iPSC中证明了IFNB1RNA (126-816倍) 和蛋白质的显著,多西环素诱导的上调.

结论:

生成的IFNB-iPSC为研究干扰素β对细胞活动和分化影响提供了强大的细胞模型.
该平台有助于开发基于细胞的新型疗法,控制局部IFN-I生产.
这项研究为深入分析IFNB1的生物作用和治疗应用提供了有价值的工具.

关键词:

在CRISPR/Cas9技术方面,杜西环素诱导基因表达的基因表达.诱导多能干细胞的诱导干细胞.干扰素-β (IFN-β) 的使用.三线化区分分化的特点

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