基于iPSC的产前的建模识别了异常囊细胞分化中的表观遗传缺陷
Robert Morey1,2,3, Tony Bui1,2,3, Virginia Chu Cheung1,2,3
1Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
iScience
|April 16, 2024
概括
孕前 (PE) 涉及到异常的 trofhoblast 发育. 这项研究在体外模拟PE外性热囊细胞 (EVT),揭示了与疾病发病有关的表观遗传变化.
科学领域:
- 生殖生物学 生殖生物学
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
背景情况:
- 孕前 (PE) 是导致母亲和胎儿并发症的主要原因之一.
- 异常的外性热囊细胞 (EVT) 发育与PE有关.
- 之前的PE相关的热囊细胞功能障碍体外模型缺乏.
研究的目的:
- 为了在体外模型PE相关的EVT功能障碍.
- 调查PE病原体背后的分子机制.
- 评估PE-EVT中的表观遗传调节.
主要方法:
- 从PE患者衍生的诱导多能干细胞 (iPSC) 衍生出的热囊细胞干细胞 (TSC) 和EVT.
- 为了进行比较分析,将原始化的iPSC转换为原始的iPSC.
- 评估EVT表面标记物 (HLA-G),入侵能力,基因表达和促进物甲基化.
主要成果:
- 原始的iPSC衍生PE-EVT表现出减少HLA-G表达和侵袭能力受损.
- 在PE-EVT中,表细胞特异性基因的表达发生变化.
- 在PE-EVT中观察到表皮细胞-介质细胞过渡通路基因的高甲基化.
结论:
- 原始的iPSC衍生的EVT可以模拟PE相关的热囊细胞异常.
- 表观遗传失调,特别是促进剂高甲基化,可能有助于PE的发病.
- 这项研究为研究PE机制提供了一个新的体外模型.
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