The G-protein-coupled receptor APJ is expressed in the second heart field and regulates Cerberus-Baf60c axis in embryonic stem cell cardiomyogenesis.

AIMS: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. METHODS AND RESULTS: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. CONCLUSION: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.

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