替代拼接CADM1与子宫内皮前体细胞功能障碍有关,而在孕前症中
Ricarda Welz1, Dhanya Ramachandran1, Bianca Schröder-Heurich1
1Gynaecology Research Unit, Department of Gynaecology and Obstetrics, Hannover Medical School, Hannover, Germany.
Physiological genomics
|February 10, 2025
概括
胎儿内皮细胞中CADM1的异常拼接与孕前有关,可能会影响后代的心血管健康. 这一发现突出了一个新的机制,有助于妊娠并发症.
科学领域:
- 心血管生物学 心血管生物学
- 遗传学和基因组学 遗传学和基因组学
- 生殖医学 生殖医学
背景情况:
- 孕前是一种与产后心血管风险相关的妊娠高血压疾病,对母亲和孩子来说都是如此.
- 带血内皮形成殖民地细胞 (ECFC) 在产前中表现出功能障碍,替代拼接失调是潜在的原因.
- 了解胎儿ECFCs中的特定分子机制对于解决孕前的长期后果至关重要.
研究的目的:
- 为了确定特定的替代拼接目标在胎儿ECFCs从生殖前怀孕.
- 调查已识别的拼接改变对ECFC行为的功能后果.
- 探索异常CADM1拼接在产前及其后代心血管病变的发病过程中的作用.
主要方法:
- 在预先 (n=16) 和正常 (n=13) 怀孕的ECFC上进行了全转录组差分拼接分析.
- 通过碎片长度分析和桑格测序验证了拼接事件.
- 在实验室中使用了与反感官形态分子的拼接切换,并对ECFCs进行了迁移和血管生成测试.
主要成果:
- 鉴定出CADM1异型ENST00000542447显著增加的丰度 (外显子8跳转) 在先兆生育ECFC中 (P=0.002).
- 证实CADM1外显子8跳转在正常的ECFC中具有类似于产前的特征.
- 证明诱导的CADM1外显子8跳转会降低ECFC迁移 (PANOVA = 0.005) 和管道形成 (PANOVA = 0.02).
结论:
- 异常的CADM1拼接,特别是异构8跳转,在胎儿的ECFCs上升调节从生育前怀孕.
- 这种拼接变化损害了ECFC功能,减少了迁移和血管生成.
- 失调的CADM1拼接可能会导致前性母亲后代的心血管后果.
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