What's in a cardiomyocyte – And how do we make one through reprogramming?

Substantial progress is being made in the field cardiac reprogramming, and those in the field are hopeful that the technology will be formulated for therapeutic use. Beyond the excitement around generating a revolutionary new approach for treating ischemic heart diseases, cardiac reprogramming has delivered provocative findings that challenge common notions of cell fate and cell identity. Have we really made de novo cardiomyocytes? To answer this question, the essential characteristics of this unique and important cell type must first be defined. In this review, we walk through the history of scientific inquiry into cardiomyocytes, and then we examine the core features of cardiomyocytes as detailed in modern definitions. Informed by this, we turn to cardiac reprogramming to analyze the various screening approaches and ultimate factor combinations used in each study. We follow this with a dissection of the evidence used to support the authors' claims of successfully creating cardiomyocytes, and we end by discussing what is known about the molecular mechanisms of cardiac reprogramming. Through this analysis, we find interesting differences between the study designs and their results, but it becomes clear that the field at large is generating cells that closely match the textbook definition cardiomyocyte. However, the differences noted between the results of each study are largely unexplained, reflecting the need for further research in both cardiac reprogramming and in native cardiomyocyte biology. Knowledge gained from future research will help move the field towards better reprogramming techniques and technologies.