Initiating Events in Direct Cardiomyocyte Reprogramming. Author Kimberly Sauls, Todd Greco, Li Wang, Meng Zou, Michelle Villasmil, Li Qian, Ileana Cristea, Frank Conlon Publication Year 2018 Type Journal Article Abstract 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. Keywords Animals, Extracellular Matrix, Transcription Factors, Protein Binding, Time Factors, Down-Regulation, Proteomics, Mice, Transgenic, Extracellular Matrix Proteins, Chromatin, Up-Regulation, Cellular Reprogramming, Myocytes, Cardiac Journal Cell Rep Volume 22 Issue 7 Pages 1913-1922 Date Published 2018 Feb 13 ISSN Number 2211-1247 DOI 10.1016/j.celrep.2018.01.047 Alternate Journal Cell Rep PMCID PMC6045814 PMID 29444441 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML