Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A.Buzzati-Traverso', CNR, Naples, Italy.
Cardiovasc Res. 2013 Oct 1;100(1):95-104. doi: 10.1093/cvr/cvt166. Epub 2013 Jun 19.
Mammalian cardiomyogenesis occurs through a multistep process that requires a complex network of tightly regulated extracellular signals, which integrate with the genetic and epigenetic machinery to maintain, expand, and regulate the differentiation of cardiac progenitor cells. Pluripotent embryonic stem cells (ESCs) recapitulate many aspects of development, and have provided an excellent opportunity to dissect the molecular mechanisms underlying cardiomyogenesis, which is still incompletely defined.
We provide new in vivo evidence that the G-protein-coupled receptor angiotensin receptor-like 1 (Apj) is expressed in the mesodermal cells of the second heart field, a population of cardiac progenitors that give rise to a major part of the definitive heart. By combining loss-and-gain of function studies in mouse ESCs, we show that Apj (i) controls the balance between proliferation and cardiovascular differentiation, (ii) regulates the Nodal/Bone Morphogenetic Protein antagonist Cerberus and the Baf60c/Smarcd3 subunit of the Brg1/Brm-associated factors (BAF) chromatin-remodelling complex.
We propose a model in which Apj controls a regulatory Cerberus-Baf60c pathway in pluripotent stem cell cardiomyogenesis, and speculate that this regulatory circuit may regulate cardiac progenitor cell behaviour.
哺乳动物的心肌发生是通过一个多步骤的过程，需要一个复杂的、受严格调控的细胞外信号网络，这些信号与遗传和表观遗传机制相整合，以维持、扩展和调节心脏祖细胞的分化。多能胚胎干细胞（ESCs）再现了许多发育方面的特征，为剖析心肌发生的分子机制提供了极好的机会，而心肌发生的分子机制仍不完全清楚。
我们提供了新的体内证据，表明 G 蛋白偶联受体血管紧张素受体样 1（Apj）在第二心脏场的中胚层细胞中表达，第二心脏场是产生大部分确定心脏的心脏祖细胞群。通过在小鼠 ESCs 中结合功能丧失和获得研究，我们表明 Apj（i）控制增殖和心血管分化之间的平衡，（ii）调节 Nodal/Bone Morphogenetic Protein 拮抗剂 Cerberus 和 Brg1/Brm 相关因子（BAF）染色质重塑复合物的 Baf60c/Smarcd3 亚基。
我们提出了一个模型，即 Apj 控制多能干细胞心肌发生中的调节 Cerberus-Baf60c 通路，并推测这个调节回路可能调节心脏祖细胞的行为。
