A retinoic acid:YAP1 signaling axis controls atrial lineage commitment.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-05-07 DOI:10.1016/j.celrep.2025.115687

Elizabeth Abraham, Aleksandra Kostina, Brett Volmert, Thomas Roule, Ling Huang, Jingting Yu, April E Williams, Emily Megill, Aidan Douglas, Olivia M Pericak, Alex Morris, Eleonora Stronati, Arantza Larrinaga-Zamanillo, Raquel Fueyo, Mikel Zubillaga, Mark D Andrake, Naiara Akizu, Aitor Aguirre, Conchi Estaras

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引用次数: 0

Abstract

In cardiac progenitor cells (CPCs), retinoic acid (RA) signaling induces atrial lineage gene expression and acquisition of an atrial cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified. To address this gap, we applied a functional genomics approach (i.e., scRNA-seq and snATAC-seq) to untreated and RA-treated human embryonic stem cell (hESC)-derived CPCs. Unbiased analysis revealed that the Hippo effectors YAP1 and TEAD4 are integrated with the atrial transcription factor enhancer network and that YAP1 activates RA enhancers in CPCs. Furthermore, Yap1 deletion in mouse embryos compromises the expression of RA-induced genes, such as Nr2f2, in the CPCs of the second heart field. Accordingly, in hESC-derived patterned heart organoids, YAP1 regulates the formation of an atrial chamber but is dispensable for the formation of a ventricle. Overall, our findings revealed that YAP1 cooperates with RA signaling to induce atrial lineages during cardiogenesis.

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A维甲酸：YAP1信号轴控制心房系承诺。

在心脏祖细胞（CPCs）中，维甲酸（RA）信号传导诱导心房系基因表达和心房细胞命运的获得。为了实现这一点，RA协调了一个尚未完全确定的下游效应物的复杂调控网络。为了解决这一差距，我们应用功能基因组学方法（即scRNA-seq和snATAC-seq）对未经处理和ra处理的人胚胎干细胞（hESC）衍生的cpc进行分析。无偏分析显示，Hippo效应子YAP1和TEAD4与心房转录因子增强子网络整合，YAP1激活心房转录因子增强子。此外，小鼠胚胎中的Yap1缺失会损害ra诱导的基因（如Nr2f2）在第二心区心肌中心细胞中的表达。因此，在hesc衍生的图案心脏类器官中，YAP1调节房室的形成，但对于心室的形成是必不可少的。总之，我们的研究结果表明，YAP1与RA信号一起在心脏发生过程中诱导心房谱系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.