Fig. 2.

Generation of cardiovascular cells from iPSCs. Somatic cells such as dermal fibroblasts or peripheral blood mononuclear cells isolated from individual patients can be reprogrammed to iPSCs via viral delivery of the four Yamanaka transcription factors (OCT4⁺, SOX2⁺). Most commonly, iPSCs are pushed to precardiac mesodermal lineage (KDR⁺, MESP1⁺) via GSK-3β inhibition, and then differentiated to cardiac progenitor cells (ISL1⁺, NKX2-5⁺) by canonical Wnt signaling inhibition. Functional cardiomyocytes (TNNT2⁺, ACTN2⁺), smooth muscle cells (CNN1⁺, MYH11⁺), or endothelial cells (CDH5⁺, PECAM1⁺) are generated by treatment with unique sets of growth factors and small molecules. Epicardial cells (WT1⁺, TBX18⁺) can also be generated from cardiac progenitor cells, which can then be differentiated to cardiac fibroblasts (POSTN⁺, DDR2⁺). Generation of endocardial cells (NFATC1⁺), either from cardiac progenitors or endothelial progenitors, is still under development. Recently, methods to generate atrial, ventricular, and nodal cardiomyocytes have been described. To date it is not clear whether specialized subtypes of endothelial cells or stromal cells can be made from iPSCs.