Résumé :
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Although our understanding of the biology of pluripotent stem cells has expanded exponentially in the past few years, the translational arm of stem cell science is in a relatively primitive state. In the cardiovascular system, a number of clinical studies have been initiated with autologous cells with a variety of delivery systems, and the early returns point to several inherent general limitations. One of the key issues relate to scalability and the generation of mature ventricular muscle cells, as well as their assembly into functional muscle tissue, from pluripotent cell lines. In this regard, recent studies in our lab in the mouse embryo have identified a multipotent, "master" islet1 cardiovascular progenitor, which contributes to all the major cell types in the murine heart. A downstream, rare committed ventricular progentior has been isolated in the islet lineage that can undergo limited selfexpansion, and will ultimately allow the generaion of a fully functional strip of mature ventricular muscle. In contrast to murine cardiogenesis, human heart development is associated with a longer onset of heart cell lineage diversification and expansion, suggesting the possibility of potentially divergent pathways. We have recently identified a diverse set of human fetal ISL1+ cardiovascular progenitor populations that give rise to the cardiomyocyte, smooth muscle, and endothelial cell lineages. In the current discussion, we examine new experimental paradigms to drive the generation and conversion of pluripotent stem cell lines towards a ventriculogenic state via epigenetic and modified RNA pathways.
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