在早期小鼠胚胎中,THAP1是通过Rrm1进行第一个细胞周期所需的母性影响因子
Qiang Fan1,2, Xi Wu1,2,3, Yanna Dang1,2
1Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, School of Life Sciences, New Cornerstone Science Laboratory, Tsinghua University, 100084, Beijing, China.
EMBO reports
|February 23, 2026
概括
坦纳托斯相关蛋白1 (Thap1) 是一种对早期哺乳动物胚胎发育至关重要的母性效应基因. 它的缺失会导致发育停止和不孕不育,因为它会损害细胞基因组激活和脱氧核酸三酸盐水平.
科学领域:
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
- 生殖生物学 生殖生物学
背景情况:
- 孕产妇效应基因 (MEGs) 对于早期胚胎发育至关重要,产生存储在卵细胞中的因素.
- 大多数已知的哺乳动物MEG编码表观遗传调节剂或RNA结合蛋白.
- 干扰MEG与生殖和先天性疾病有关.
研究的目的:
- 确定涉及早期哺乳动物发育的新型母性效应基因.
- 为了研究转录因子Thanatos相关蛋白1 (Thap1) 作为母体效应基因的作用.
主要方法:
- 使用小鼠模型进行卵细胞特异性基因删除.
- 早期胚胎发育和进展 (1细胞到2细胞阶段) 的分析.
- 评估杂虫基因组激活 (ZGA).
- 低输入代谢组分析以测量脱氧核酸三酸盐 (dNTP) 水平.
- 通过Rrm1.1的过度表达进行基因救援实验.
主要成果:
- 蛋细胞特异的Thap1删除导致胚胎进展延迟和1-2细胞停止.
- Thap1 缺乏症会损害雄性基因组激活 (ZGA) 和女性生育能力.
- THAP1调节关键基因,包括Rrm1,对于dNTP合成至关重要.
- 在卵细胞转化为胚胎的过程中观察到THAP1依赖的dNTP积累.
- Rrm1过度表达在Thap1缺乏的胚胎中挽救了发育缺陷.
结论:
- THAP1被确定为一种关键的母性效应基因,对哺乳动物卵细胞功能和早期胚胎生成至关重要.
- THAP1通过Rrm1调节dNTP水平,这对于成功激活和发育胚胎基因组至关重要.
- 这项研究强调了THAP1在母亲对早期胚胎发育的控制中不可或缺的作用.
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