通过调节CDX2,KAT8介导的H4K16ac对维持热囊细胞自我更新和增殖至关重要
Shilei Bi1,2,3,4, Lijun Huang1,2,3,4, Yongjie Chen5
1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
Nature communications
|July 3, 2024
概括
由于KAT8基因组乙转移酶的驱动,细胞干的调节失调,导致流产. 准KAT8-H4K16ac-CDX2通路可能为复发性流产提供新的治疗方法.
科学领域:
- 生殖生物学 生殖生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发展生物学 发展生物学
背景情况:
- 异常的 trofhoblast 功能是流产的主要原因.
- 控制热细胞自我更新和分化的调节机制尚未完全理解.
研究的目的:
- 调查KAT8在热囊细胞发育中的作用及其与重复流产 (RPL) 的联系.
- 探索针对RPL中的KAT8-H4K16ac-CDX2轴的治疗潜力.
主要方法:
- 在小鼠中,Kat8的热囊细胞特异性缺失.
- 在热原体干细胞 (TSC) 中进行RNA测序 (RNA-seq) 和CUT&Tag分析.
- 在体外研究中使用热囊细胞器官和SIRT1.1的药理抑制.
主要成果:
- 热囊细胞中的Kat8缺失导致胚胎致死性和胚胎外外皮缺陷.
- KAT8对H4K16进行乙化,以调节CDX2的表达,这是一个关键的 trofhoblast 茎度标志物.
- 降低的KAT8,CDX2和H4K16ac水平与RPL相关;EX527治疗改善了患者衍生器官的胎盘缺陷.
结论:
- KAT8-H4K16ac-CDX2通路对于胎盘发育和热囊细胞自我更新至关重要.
- 针对这种表观遗传轴,为复发性流产提供了一个潜在的治疗策略.
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