通过NAT10介导的N4-乙基提丁mRNA修饰调节了人类胚胎干细胞的自我更新
Rucong Liu1,2, Zibaguli Wubulikasimu1, Runze Cai1
1Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking University, Beijing 100191, China.
Nucleic acids research
|July 27, 2023
概括
酶NAT10及其N4-乙基 (ac4C) 修饰对于通过稳定关键转录,影响自我更新和分化来维持人类胚胎干细胞 (hESC) 多能性至关重要.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- N4-乙基丁 (ac4C) 是一种被NAT10催化后的转录后RNA修饰,已知会影响mRNA稳定性.
- 在哺乳动物发育和多能性中,ac4C和NAT10的作用尚不清楚.
研究的目的:
- 研究NAT10催化ac4C修饰在人类胚胎干细胞 (hESC) 多能性的作用.
- 探索NAT10表达,ac4C水平和hESC中自我更新的维持之间的关系.
主要方法:
- 高通量ac4C向的RNA免疫沉测序 (ac4C-RIP-seq) 的高通量ac4C向的RNA免疫沉测序.
- 以NaCNBH3为基础的化学ac4C测序 (ac4C-seq).
- 液体染色学-双重质谱法 (LC-MS/MS). 这是一个很好的方法.
- 在hESCs中对NAT10的遗传失活化.
主要成果:
- 在hESCs中,NAT10表达与多能性正相关.
- 在hESC转录组中检测到显著的ac4C修饰,特别是在核心多能性因子的转录上.
- NAT10无活化降低了ac4C水平,增加了OCT4转录衰变,损害了hESC自我更新,并促进了分化.
结论:
- 为了保持hESC多能性,NAT10催化ac4C的修饰是必不可少的.
- 多能转录网络和ac4CRNA表观遗传修饰之间存在相互连接,用于hESC自我更新.
- 这项研究揭示了一种新的表观遗传机制,调节干细胞命运.
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