通过改造的SOX1717来改善多能诱导和维护的决定因素的评估
Haoqing Hu1, Derek Hoi Hang Ho1,2, Daisylyn Senna Tan1
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Nucleic acids research
|August 22, 2023
概括
与SOX2.2相比,一个工程 SOX17 变体,SOX17FNV,显著增强多能诱导. 这项研究揭示了SOX17FNVV.
科学领域:
- 干细胞生物学 干细胞生物学
- 多能性的分子机制.
- 合成生物学 合成生物学
背景情况:
- SOX2是维持多能性的关键转录因子.
- 野生类型的SOX17不能诱导多能性.
- 工程SOX因子诱导多能性的机制在很大程度上是未知的.
研究的目的:
- 阐明工程SOX17变体 (SOX17FNV) 强烈诱导多能性的机制.
- 为了比较SOX17FNV的重编程效率与SOX2.
- 确定SOX17FNV负责其活动的关键领域.
主要方法:
- 在体外结合测试中使用核细胞核颗粒.
- 同免疫沉和DNA结合测试以评估蛋白质-DNA相互作用.
- 在小鼠和人类细胞中进行细胞重编程实验.
- 对SOX17FNV进行系统的删除分析.
主要成果:
- 在诱导小鼠和人类细胞中的多能性方面,SOX17FNV的性能优于SOX2.
- SOX17FNV比SOX2更能将OCT4与正规DNA元素结合在一起.
- 与SOX2.2相比,SOX17变种表现出增强的相位分离和自我组织.
- 一个最小的SOX17FNV (miniSOX) 保持了高的重编程活动.
结论:
- SOX17FNV增强的多能诱导是由与OCT4合作的DNA结合和改进的自我组织介导的.
- SOX17FNV的C端对其重编程功能至关重要.
- 像SOX17FNV这样的工程SOX因子代表了细胞工程和重编程的强大工具.
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