Gene expression in mouse neonatal cardiomyocytes, cardiac fibroblasts, reprogramming failed GFP- cells, and GFP+ iCMs

The reprogramming of fibroblast cells to induced pluripotent stem (iPS) cells raises the possibility that a somatic cell could be reprogrammed to an alternative differentiated fate without first becoming a stem/progenitor cell. A large pool of fibroblast cells exists in the post-natal heart, yet no single “master regulator” of direct cardiac reprogramming has been identified. Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c and Tbx5) rapidly and efficiently reprogrammed post-natal cardiac or tail-tip fibroblasts directly into differentiated cardiomyocyte-like cells. Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously. Fibroblast cells transplanted into mouse hearts one day after transduction of the three factors also differentiated into cardiomyocyte-like cells. These findings demonstrate that functional cardiomyocytes can be directly reprogrammed from differentiated somatic cells by defined factors. Reprogramming of endogenous or explanted fibroblast cells might provide a source of cardiomyocytes for regenerative approaches. To compare the progressive global gene expression pattern of iCMs, cardiomyocytes and cardiac fibroblasts, we isolated RNA from mouse neonatal cardiomyocytes, cardiac fibroblasts, reprogramming failed GFP- cells and GFP+ iCMs, and profiled mRNA expressions by microarray analyses. Arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates for each group.