Molecular Signature of Stem Cells Undergoing Cardiomyogenic Differentiation

Cardiomyocytes (CMs) are mitotically inactive but metabolically highly active cells that constitute a major population in the heart. The cumbersome isolation and purification protocols combined with the difficulty in their in vitro propagation as a primary culture remain the major impediments in their biological characterization. Therefore, understanding the molecular events that drive the successful differentiation of stem cells to become morphofunctionally competent CMs via advanced cellular technology is essential to better manipulate them for human applications. Cardiomyogenic differentiation of stem cells is relatively inefficient with a limited success rate due to the complexity of the molecular circuit involved therein. Akin to the embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) have vast prospective to give rise to any type of cell from the three germ layers without ethical concerns. Mesenchymal stem cells have limited differentiation potential toward cardiomyocyte lineage. Given their developmental aspects, the epigenomic signature often directs the cell’s function which in turn governs their expression profile. Such epigenetic mechanisms include DNA methylation, histone core modifications, and miRNA regulations, which are associated with gene expression or silencing in the cell’s progression toward a CM’s fate. This chapter elucidates in-depth the regulatory process underlying CMs’ differentiation at the genetic as well as epigenetic levels via themodulation of chromatin architecture. Specifically in this chapter, we will elaborate on the gene circuit and their expression profile in the various stem cells, heading toward cardiomyocyte lineage under different culture technologies from 2D, 3D, and even up to the single-cell level.