孕产妇TDP43在小鼠卵细胞转化为胚胎过程中协调核斑组合和胚胎拼接激活
Zuo-Qi Deng1, Zhi-Yan Jiang1, Yu-Ke Wu1
1Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Nucleic acids research
|January 12, 2026
概括
在胚胎早期发育过程中,TDP43调节核斑点 (NS) 进行胚胎剪接激活 (ZSA). 它的正确功能对于正常发育至关重要,防止2细胞停止并维持细胞多能性.
科学领域:
- 发展生物学 发展生物学
- 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.
背景情况:
- 紫芽拼接激活 (ZSA) 对于早期胚胎发育至关重要,但其调节的理解很少.
- 核斑点 (NS) 是关键的剪接区域,在小鼠的2细胞阶段新形成,与ZSA相吻合.
研究的目的:
- 研究TARDNA结合蛋白-43 (TDP43) 在早期胚胎发生过程中调节NS组合和ZSA的作用.
- 阐明TDP43影响拼接和胚胎发育的机制.
主要方法:
- 在小鼠胚胎中观察NS和TDP43的局部化.
- 在二细胞胚胎中分析TDP43的功能状态 (凝结缺陷形式).
- 研究TDP43与RNA和NS蛋白的相互作用.
- 研究母体TDP43缺乏和子宫外TDP43表达对NS,ZSA和胚胎发育的影响.
主要成果:
- TDP43与NS具有部分相邻且相互排斥的局部化.
- 在NS调节中,TDP43的凝结缺陷状态是活跃的.
- TDP43与NS相关的RNA和蛋白质相互作用.
- 缺少TDP43或过度表达会破坏NS组合和ZSA,导致2细胞停止和多能性受损.
- 双向破坏ZSA会导致发育停滞.
结论:
- TDP43被确定为NS组件和ZSA的关键上游调节器.
- 保持TDP43的平衡对于早期胚胎的正常转录后调节至关重要.
- 这项研究为管理ZSA和早期胚胎发育的机制提供了新的见解.
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