Transcriptome transfer provides a model for understanding the phenotype of cardiomyocytes

We show that the transfer of the adult ventricular myocyte (AVM) transcriptome into either a fibroblast or an astrocyte converts the host cell into a cardiomyocyte. Transcriptome-effected cardiomyocytes (tCardiomyocytes) display morphologies, immunocytochemical properties, and expression profiles of postnatal cardiomyocytes. Cell morphology analysis shows that tCardiomyoctes are elongated and have a similar length-to-width ratio as AVMs. These global phenotypic changes occur in a time-dependent manner and confer electroexcitability to the tCardiomyocytes. tCardiomyocyte generation does not require continuous overexpression of specific transcription factors; for example, the expression level of transcription factor Mef2c is higher in tCardiomyocytes than in fibroblasts, but similar in tCardiomyocytes and AVMs. These data highlight the dominant role of the gene expression profile in developing and maintaining cellular phenotype. The transcriptome-induced phenotype remodeling-generated tCardiomyocyte has significant implications for understanding and modulating cardiac disease development.