Tcf21 regulates the specification and maturation of proepicardial cells
Tcf21 regulates the specification and maturation of proepicardial cells
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DOI：
10.1242/dev.093385
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发表时间：
2013-06-01
期刊：
影响因子：
4.6
通讯作者：
Conlon, Frank L.
中科院分区：
文献类型：
--
作者：
Tandon, Panna;Miteva, Yana V.;Conlon, Frank L.
心外膜是脊椎动物心脏发育所必需的间皮细胞层，与成人心脏损伤后的修复有关。心外膜最初形成于一个动态的前体结构，即心外膜器官，细胞从该器官迁移到心脏表面。在心外膜发育的初始阶段，认为决定了关键的心外膜衍生细胞谱系。在这里，我们定义了一个基本的要求，转录因子Tcf21在非洲爪蟾心外膜发育的早期阶段，并表明，Tcf21的耗尽导致破坏proepicardial细胞规格和未能形成一个成熟的上皮心外膜。使用基于质谱的方法，我们定义了Tcf21的相互作用，并建立了其与作为转录辅助抑制因子的蛋白质的关联。此外，使用基于体内系统的方法，我们确定了一组以前未报告的前心外膜前体基因，这些基因在Tcf21耗尽时在心外膜层中持续表达，从而证实了Tcf21在正确确定前心外膜谱系中的主要作用。总的来说，这些研究使我们提出，Tcf21作为一个转录抑制因子的功能，以调节前心外膜细胞的规范和正确形成一个成熟的上皮心外膜。
The epicardium is a mesothelial cell layer essential for vertebrate heart development and pertinent for cardiac repair post-injury in the adult. The epicardium initially forms from a dynamic precursor structure, the proepicardial organ, from which cells migrate onto the heart surface. During the initial stage of epicardial development crucial epicardial-derived cell lineages are thought to be determined. Here, we define an essential requirement for transcription factor Tcf21 during early stages of epicardial development in Xenopus, and show that depletion of Tcf21 results in a disruption in proepicardial cell specification and failure to form a mature epithelial epicardium. Using a mass spectrometry-based approach we defined Tcf21 interactions and established its association with proteins that function as transcriptional co-repressors. Furthermore, using an in vivo systems-based approach, we identified a panel of previously unreported proepicardial precursor genes that are persistently expressed in the epicardial layer upon Tcf21 depletion, thereby confirming a primary role for Tcf21 in the correct determination of the proepicardial lineage. Collectively, these studies lead us to propose that Tcf21 functions as a transcriptional repressor to regulate proepicardial cell specification and the correct formation of a mature epithelial epicardium.