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Transcriptional Control of Cell Lineage Development in Epicardium-Derived Cells
The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way ML 7020, Cincinnati, OH 45229, USA
* Author to whom correspondence should be addressed.
Received: 16 May 2013; in revised form: 19 June 2013 / Accepted: 20 June 2013 / Published: 3 July 2013
Abstract: Epicardial derivatives, including vascular smooth muscle cells and cardiac fibroblasts, are crucial for proper development of the coronary vasculature and cardiac fibrous matrix, both of which support myocardial integrity and function in the normal heart. Epicardial formation, epithelial-to-mesenchymal transition (EMT), and epicardium-derived cell (EPDC) differentiation are precisely regulated by complex interactions among signaling molecules and transcription factors. Here we review the roles of critical transcription factors that are required for specific aspects of epicardial development, EMT, and EPDC lineage specification in development and disease. Epicardial cells and subepicardial EPDCs express transcription factors including Wt1, Tcf21, Tbx18, and Nfatc1. As EPDCs invade the myocardium, epicardial progenitor transcription factors such as Wt1 are downregulated. EPDC differentiation into SMC and fibroblast lineages is precisely regulated by a complex network of transcription factors, including Tcf21 and Tbx18. These and other transcription factors also regulate epicardial EMT, EPDC invasion, and lineage maturation. In addition, there is increasing evidence that epicardial transcription factors are reactivated with adult cardiac ischemic injury. Determining the function of reactivated epicardial cells in myocardial infarction and fibrosis may improve our understanding of the pathogenesis of heart disease.
Keywords: transcription factor; Wt1; Tcf21; Tbx18; epicardium derived cell; embryo; cardiovascular disease
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Braitsch, C.M.; Yutzey, K.E. Transcriptional Control of Cell Lineage Development in Epicardium-Derived Cells. J. Dev. Biol. 2013, 1, 92-111.
Braitsch CM, Yutzey KE. Transcriptional Control of Cell Lineage Development in Epicardium-Derived Cells. Journal of Developmental Biology. 2013; 1(2):92-111.
Braitsch, Caitlin M.; Yutzey, Katherine E. 2013. "Transcriptional Control of Cell Lineage Development in Epicardium-Derived Cells." J. Dev. Biol. 1, no. 2: 92-111.