心脏发育过程中的细胞命运转变及命运决定

Cell Fate Transition and Determination in Heart Development

胚胎发育过程中,心脏发生起源于生心中胚层(cardiac mesoderm)。在小鼠早期胚胎(E6.5),上胚体(epiblast)在低浓度Nodal诱导下,Eomes出现并激活Mesp1表达。Mesp1作为主调控者(master regulator),激活一系列生心关键转录因子及生心特异基因的表达,促进生心祖细胞的特化及生心区(cardiac field)的形成。之后的心脏形态发生涉及细胞命运的转变,包括流出道分隔过程中神经嵴细胞向间充质细胞转变、内皮细胞向间充质转变及房室通道发育过程中的内皮细胞向间充质转变。最新的研究表明,流出道在分隔成为主动脉和肺动脉根部之前,其中的细胞命运已经被预先设定。此综述文章重点探讨生心祖细胞特化、细胞命运转变与命运预先设定等方面的新进展,调控机制及争议问题。

Cardiogenesis originates from the cardiac mesoderm during early embryonic development. In the murine embryo, the transcription factor Eomes appears to activate the transcription of Mesp1 in the epiblast at E6.5. Mesp1 as a master regulator, induces a panel of cardiac specific transcription factors as well as other cardiac genes that are essential for heart development, which facilitates the specification of cardiac progenitors and formation of the cardiac field. Subsequently, cardiac morphogenesis involves cell fate transition including neural crest cell transition into mesenchymal cells during OFT(outflow tract) septation and EnMT(endothelial to mesenchymal transition) in atrio-ventricular canal development. The latest study demonstrates that the cell fate has been pre-determined prior to OFT septation into the base of aorta and pulmonary artery. In this review, we discuss the new findings of cardiac specification, cell fate transition and pre-determination with underlying regulatory mechanisms. Meanwhile, some special issues of controversy will be introduced.