VGLL1对正在发育的热囊细胞区的转录组和表观基因组都有贡献
Ruben I Calderon1,2, Nirvay Sah1, Molly Huang3
1Department of Pathology, University of California San Diego, La Jolla, CA 92093.
概括
VGLL1对于人体体外皮 (TE) 发育至关重要,整合了像BMP和WNT这样的关键信号通路. 这种协同激活剂通过调节基因表达和表观遗传修饰来加强热囊细胞的身份,以成功植入.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 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:
- 托菲克托皮 (TE) 是哺乳动物发育中的第一个血统,对于植入和胎盘形成至关重要.
- 虽然已知像BMP,WNT和HIPPO这样的保存途径,但由于物种差异,需要针对人类的特定模型.
- 此前,VGLL1已被确定为人类特异性的胎盘标记物和TEAD转录因子的联合激活剂.
研究的目的:
- 通过基于多能干细胞 (PSC) 的模型,研究人类TE形成期间的染色质重塑和转录动态.
- 阐明VGLL1在确定热囊细胞身份和在早期人类发育过程中整合信号通路中的作用.
主要方法:
- 使用BMP4诱导的多能干细胞 (PSC) 模型进行体皮 (TE) 诱导.
- 使用向测试分析了染色质可访问性,基因表达和表观遗传修饰 (H3K27me3).
- 研究了VGLL1对TE转录因子,信号通路 (WNT) 和表观遗传修饰剂 (KDM6B) 的调节功能.
主要成果:
- 诱导BMP4促进了 trofhoblast 基因表达和染色质可访问性,在WNT激活时具有过渡性中皮体标志物.
- 在GATA2/3和TFAP2A/C的下游,VGLL1对于完全的热囊细胞身份至关重要,可以调节EGFR并加强GATA3.
- VGLL1直接调节WNT信号组件,并准KDM6B,一个激素脱甲基酶,激活TE相关的双价促进体.
结论:
- VGLL1作为人类TE规范中的中央调节器,集成HIPPO,BMP和WNT信号.
- VGLL1通过积极的反循环和通过KDM6B的表观遗传调节来确定 trofhoblast 的身份.
- 这项研究为人类TE发展提供了一个机制框架,强调了VGLL1的关键作用.
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