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一个视网膜酸:YAP1信号轴控制着心房血统的承诺
Elizabeth Abraham1, Aleksandra Kostina2, Brett Volmert2
1Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
视网红酸 (RA) 信号引导心脏原生细胞向心房命运. 河马通路效应器YAP1与RA信号合作,激活心房增强剂并促进心房腔的发育.
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
- 心血管研究研究心血管研究
背景情况:
- 网红酸 (RA) 信号传递对于诱导心房血统基因表达和心脏原生细胞 (CPC) 中的细胞命运至关重要.
- 控制这一过程的RA信号下游的精确监管网络尚未完全理解.
研究的目的:
- 为了识别人类胚胎干细胞 (hESC) 衍生的CPC中RA信号的新型下游作用因子.
- 阐明Hippo通路,特别是YAP1和TEAD4在RA中介性心房系谱规范中的作用.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 和单核ATAC测序 (snATAC-seq) 在hESC衍生的CPC上使用.
- 功能性基因组学方法用于分析基因表达和染色质可访问性.
- 在小鼠胚胎中的Yap1删除和hESC衍生的心脏器官模型被用于体内和体外验证.
主要成果:
- 无偏见的分析确定了YAP1和TEAD4作为集成到心房转录因子网络的关键Hippo通路影响者.
- YAP1被证明可以激活CPC中的RA反应增强剂,促进RA诱导的基因如Nr2f2.2的表达.
- 在小鼠胚胎中Yap1缺失导致RA诱导的基因表达在第二心场CPC中受损,在hESC衍生的有机体中YAP1调节了心房形成.
结论:
- 在心脏发生过程中,YAP1作为RA信号传递的关键调解者,在引入心房血统过程中发挥关键作用.
- YAP1与RA信号合作,确定心房细胞命运和调节心房腔发育,但对于心室形成是不可或缺的.
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