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在小鼠体质重编程过程中,在单细胞水平上对A-to-IRNA编辑进行分析
Tianhang Lv1,2, Siyuan Jiang1,2, Xiaoshan Wang2
1College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
Heliyon
|July 31, 2023
概括
在重编程过程中,单个细胞中的腺至氨酸 (A-to-I) RNA编辑在单个细胞中具有动态变化. 这种由ADAR1调节的RNA编辑影响基因表达,并促进介质细胞-上皮细胞过渡.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 干细胞生物学 干细胞生物学
背景情况:
- 体细胞重编程成诱导多能干细胞 (iPSCs) 是一个复杂的,异质的过程.
- 腺至氨酸 (A-to-I) RNA编辑是影响细胞重编程的关键生物因素.
- 在单细胞水平上了解RNA编辑的动态对于破译重编程机制至关重要.
研究的目的:
- 在单细胞重编程过程中研究A-to-IRNA编辑的作用和动态.
- 在这个过程中识别受A-to-IRNA编辑影响的特定基因和通路.
- 为了将RNA编辑水平与RNA编辑酶如ADAR1.1的表达相关联.
主要方法:
- 使用高深度,全长单细胞RNA测序 (scRNA-seq) 数据对A-to-IRNA编辑部位的分析.
- 在单细胞水平上量化A-to-IRNA编辑频率.
- 基因本体学 (GO) 丰富分析以确定受影响的途径.
- 在RNA编辑水平和基因表达之间的相关性分析.
主要成果:
- A-to-I RNA编辑频率在重新编程过程中表现出显著的细胞对细胞变异和动态变化.
- A-to-I RNA编辑水平与RNA编辑酶ADAR1.1的表达呈正相关.
- 基于ADAR1的A-to-I编辑降低了特定的基因 (例如Igtp,Irgm2) 的调节,以抑制干扰素-β反应和蛋白质复合体稳定通路,促进介质细胞-上皮细胞过渡 (MET).
- 在A-to-I编辑频率和像Nras和Ube2l6这样的基因表达之间观察到负相关性.
结论:
- A-to-I RNA编辑是单细胞重编程中的一个动态调节机制.
- 通过调节基因表达和细胞通路,ADAR1介导的RNA编辑在促进MET方面发挥着关键作用.
- 这些发现为管理细胞重编程和多能诱导的分子机制提供了新的见解.
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