A myocardial lineage derives from Tbx18 epicardial cells

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Abstract
Knowledge of the nature of cardiac progenitor cells is important for an understanding of the development of heart diseases, and as a potential route to regenerative therapy using stem cells. Two groups now report previously unknown cardiac myocyte lineages isolated from the proepicardium of the mouse. Cai et al. identify a population of progenitor cells that express the transcription factor Tbx18, and Zhou et al. identify cells marked by the transcription factor Wt1. Both types of progenitor are pluripotent, capable of producing several different classes of heart cell, making them promising candidates for use in cardiac repair. This paper identifies a novel population of progenitor cells that come from the pro-epicardial organ. These cells, which express the transcription factor Tbx18, migrate to the outer surface of the heart to form the epicardium, and they also contribute to myocytes in the ventrical septum and atrial and ventricular walls, as well as to cardiac fibroblasts and coronary smooth muscle cells. Thus these progenitors seem to be pluripotent. Understanding the origins and roles of cardiac progenitor cells is important for elucidating the pathogenesis of congenital and acquired heart diseases1,2. Moreover, manipulation of cardiac myocyte progenitors has potential for cell-based repair strategies for various myocardial disorders3. Here we report the identification in mouse of a previously unknown cardiac myocyte lineage that derives from the proepicardial organ. These progenitor cells, which express the T-box transcription factor Tbx18, migrate onto the outer cardiac surface to form the epicardium, and then make a substantial contribution to myocytes in the ventricular septum and the atrial and ventricular walls. Tbx18-expressing cardiac progenitors also give rise to cardiac fibroblasts and coronary smooth muscle cells. The pluripotency of Tbx18 proepicardial cells provides a theoretical framework for applying these progenitors to effect cardiac repair and regeneration.