ESTABLISHMENT OF THE MESODERMAL CELL-LINE QCE-6 - A MODEL SYSTEM FOR CARDIAC CELL-DIFFERENTIATION

The QCE-6 cell line was derived from precardiac mesoderm of the Japane se quail. As previously reported, these cells are able to differentiat e into two distinct cardiac cell types with myocardial or endocardial endothelial cell properties. This present communication describes in d etail the derivation of this cell line and further characterizes the n ontreated and induced myocardial and endothelial phenotypes of these c ells. The QCE-6 cells exhibit an epithelial morphology, as well as the pattern of protein expression, that is characteristic of precardiac m esoderm. Treatment with retinoic acid, basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-beta 2, and TGF-beta 3 induce s these cells to differentiate and produce mixed cultures of epithelia l and mesenchymal cells. The epithelial cells express myosin, desmin, and cardiac troponin I in a punctate pattern throughout the cytoplasm. These sarcomeric proteins become organized in a premyofibrillar patte rn when TGF-beta 1, platelet-derived growth factor (PDGF)-BB, and insu lin-like growth factor (IGF) II are added in combination along with re tinoic acid, bFGF, TGF-beta 2, and TGF-beta 3. Also, these treatments induce N+,(+)-ATPase expression. When the QCE-6 cells are cultured on collagen type I, the mesenchymal cells that are promoted by retinoic a cid, bFGF, TGF-beta 2, and TGF-beta 3 will invade the gel. These mesen chymal cells are positive for QH1 and JB3, which are both markers for presumptive endocardial cells within the early cardiogenic mesoderm. T he addition of both PDGF-BB and IGF II to QCE-6 cell cultures will inh ibit the ability of retinoic acid, bFGF, TGF-beta 2, and TGF-beta 3 to induce both the mesenchymal morphology and QH1 and JB3 expression. Co llectively, these results suggest that the process of cardiac cell dif ferentiation is regulated by multiple signals and that early cardiogen ic mesoderm contains a bipotential stem cell that can give rise to bot h the myocardial and endocardial lineages. More important, since the Q CE-6 cells are representative of early cardiogenic cells, this cell li ne offers a unique model system to study cardiac cell differentiation.