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单细胞分析识别了小鼠多能转化为2C类转变和体细胞重编程中的LIN28AmRNA点

Jieyi Hu¹, Jianwen Yuan², Quan Shi³

¹Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China.

The Journal of biological chemistry

|September 29, 2024

概括

像LIN28A这样的RNA结合蛋白对细胞身份至关重要. 这项研究揭示了LIN28A.

科学领域:

分子生物学分子生物学
干细胞生物学干细胞生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

RNA结合蛋白 (RBPs) 是细胞过程的关键调节者,包括干细胞多能性和发育.
LIN28A是一种关键的多能性调节剂,已知可以控制microRNA成熟和mRNA翻译/稳定性,但其在特定细胞状态中的mRNA标仍然不完全理解.
在单细胞水平上了解RBP-RNA相互作用对于破译复杂的生物过程,如细胞重编程和全能性至关重要.

研究的目的:

在小鼠胚胎干细胞 (ESC),双细胞胚胎样细胞 (2CLC) 和体细胞重编程过程中,对RNA结合蛋白LIN28A的mRNA标进行分析.
阐明LIN28A在细胞重编程过程中维持全能性和促进多能性获得中的作用.
在单细胞分辨率下研究LIN28A介导的RNA调节.

主要方法:

通过编辑识别的RBPs目标 (TRIBE) 的应用,具有单细胞分辨率 (scTRIBE) 来映射LIN28A结合的mRNAs.
对 scTRIBE 数据集的量化单细胞分析.
在体细胞重编程过程中对LIN28A-mRNA网络的分析.

主要成果:

在2CLC中观察到LIN28A与编码核糖体生物发生因子和全能因子的mRNA结合的显著增加.
发现LIN28A可以延长特定的与全能相关的mRNA的半衰期,这表明它在维持全能状态方面发挥了作用.
在特定的重编程轨迹中确定了不同的LIN28A-mRNA网络,与介质细胞到上皮细胞过渡和多能性获得相关.

结论:

林28A在调节干细胞状态方面发挥着多方面的作用,超出了其在微RNA处理中的已知功能.
林28A与特定mRNA的相互作用对于保持全能性和促进细胞重编程至关重要.
单细胞分辨率的RNA蛋白相互作用提供了关键的洞察力,对基因表达在干细胞和重编程的动态调节.

关键词:

在 LIN28A 中,RNA结合蛋白质是RNA结合的蛋白质.RNA与蛋白质的相互作用部落部落部落部落多能性的多能性.重编程是重新编程.完全强大的能力.

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