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对内心切口的合作反应揭示了与河马通路的相互作用
Luis Luna-Zurita1,2, Brenda Giselle Flores-Garza1,2, Dimitrios Grivas1,2,3
1Intercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (L.L.-Z., B.G.F.-G., D.G., M.S.-A., J.L.d.l.P.).
Circulation research
|November 14, 2023
概括
缺口信号通过控制内心的非编码元素来调节心脏膜的发育. 本研究确定了关键的调节区域和参与门形成和疾病的因素.
科学领域:
- 心血管生物学 心血管生物学
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
背景情况:
- 内心脏对于心脏膜的发育和成熟至关重要.
- 遗传研究将内心基因与双主动脉和性主动脉疾病联系起来.
- 了解门开发中的非编码监管要素和上游因素是有限的.
研究的目的:
- 调查Notch信号在心脏门发育期间调节内心脏基因表达和染色质可访问性的作用.
- 识别控制内心脏基因活性的非编码调节元素及其相关因素.
- 探索Notch和Hippo通路在内心发育和疾病中的相互作用.
主要方法:
- 在小鼠胚胎内心细胞中通过培和抑制操纵的Notch信号.
- 分析了转录形状和染色质可访问性景观.
- 集成的多omics数据集 (转录组,蛋白组,染色体可访问性,转录因子占用).
- 生成了CRISPR-Cas9编辑模型以验证非编码的监管元素.
主要成果:
- 确定了胚胎内心对诺奇配体的初级和二级转录反应.
- 定义了与门发育和疾病相关的NOTCH依赖的转录特征.
- 通过整合色素可访问性数据,发现了潜在的非编码监管元素.
- 已验证的候选监管要素和拟议的相互作用辅因子.
- 通过Yap抑制观察到与Hippo通道的合作抑制.
结论:
- 痕信号编排了胚胎内心的顺序转录调节.
- 口激活特定的非编码元素,并抑制那些对门发育有害的元素.
- 这项研究提供了关于心脏门发育和疾病的调节机制的见解.
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