TMT analysis of early proteome events in direct cardiomyocyte reprogramming

Direct reprogramming of fibroblasts into cardiomyocyte-like cells (iCM) holds great potential for heart regeneration and disease modeling and may lead to future therapeutic applications in human patients with heart disease. Currently, the application of this technology is limited by our lack of understanding of the molecular mechanisms which drive direct iCM reprogramming. Using a quantitative mass spectrometry-based proteomic approach we have identified the temporal global changes in protein abundance that occur during the initial phases of iCM reprogramming. Collectively, our results show systematic and temporally distinct alterations in the levels of specific functional classes of proteins during the initiating steps of reprogramming including extracellular matrix proteins, translation factors, and chromatin-binding proteins.