Initiating 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. Currently, application of this technology is limited by our lack of understanding of the molecular mechanisms that drive direct iCM reprogramming. Using a quantitative mass spectrometry-based proteomic approach, we identified the temporal global changes in protein abundance that occur during initial phases of iCM reprogramming. Collectively, our results show systematic and temporally distinct alterations in levels of specific functional classes of proteins during the initiating steps of reprogramming including extracellular matrix proteins, translation factors, and chromatin-binding proteins. We have constructed protein relational networks associated with the initial transition of a fibroblast into an iCM. These findings demonstrate the presence of an orchestrated series of temporal steps associated with dynamic changes in protein abundance in a defined group of protein pathways during the initiating events of direct reprogramming.
['Sauls|Kimberly|K|', 'Greco|Todd M|TM|', 'Wang|Li|L|', 'Zou|Meng|M|', 'Villasmil|Michelle|M|', 'Qian|Li|L|', 'Cristea|Ileana M|IM|', 'Conlon|Frank L|FL|']
D000818:Animals D065150:Cellular Reprogramming D002843:Chromatin D015536:Down-Regulation D005109:Extracellular Matrix D016326:Extracellular Matrix Proteins D008822:Mice, Transgenic D032383:Myocytes, Cardiac D011485:Protein Binding D040901:Proteomics D013997:Time Factors D014157:Transcription Factors D015854:Up-Regulation
direct reprogramming iCM heart cardiac induced cardiomyocytes quantitative mass spectrometry