依赖METTL3的m6ARNA甲基化调节了可转移的元素,并通过可转移的元素衍生增强剂抑制了人类的原始多能性
Weiyu Zhang1,2, Haifeng Fu3, Yunying Huang3
1Centre for Translational Stem Cell Biology, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Nucleic acids research
|April 29, 2025
概括
酶METTL3对于维持人类多能干细胞 (hPSC) 至关重要,与小鼠细胞不同. 由于激活可转移元素,METTL3的损失会破坏多能性并损害分化.
科学领域:
- 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
- 在RNA生物学,RNA生物学.
背景情况:
- N6-甲基氨酸 (m6A) 是最丰富的mRNA修饰,调节基因表达.
- METTL3是主要催化m6A的酶.
- 已知小鼠胚胎干细胞 (mESCs) 中的m6A功能,但其在人类多能干细胞 (hPSCs) 中的作用不明.
研究的目的:
- 调查METTL3在hPSC维护和多能性中的作用.
- 阐明METTL3调节hPSCs的分子机制.
主要方法:
- 在hPSC中使用了一种METTL3可诱导淘汰 (iKO) 系统.
- 分析了多能性因子表达和差异化能力.
- 研究了对可转移元素 (TE) 表达和染色质状态的影响.
主要成果:
- 与mESC不同的是,METTL3对于hPSC维护至关重要.
- METTL3损失上调了多能性因子和差异化受损.
- METTL3缺乏激活了灵长类动物特异性TEs (SVA_D,HERVK/LTR5_Hs),影响染色体和基因表达.
结论:
- 依赖METTL3的m6A甲基化对于抑制hPSC中的TE表达至关重要.
- METTL3通过控制TE介导的基因激活来调节人类的多能性网络.
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