Initiating Events in Direct Cardiomyocyte Reprogramming.

TitleInitiating Events in Direct Cardiomyocyte Reprogramming.
Publication TypeJournal Article
Year of Publication2018
AuthorsSauls, K, Greco, TM, Wang, L, Zou, M, Villasmil, M, Qian, L, Cristea, IM, Conlon, FL
JournalCell Rep
Date Published2018 Feb 13
KeywordsAnimals, Cellular Reprogramming, Chromatin, Down-Regulation, Extracellular Matrix, Extracellular Matrix Proteins, Mice, Transgenic, Myocytes, Cardiac, Protein Binding, Proteomics, Time Factors, Transcription Factors, Up-Regulation

<p>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.</p>

Alternate JournalCell Rep
PubMed ID29444441
PubMed Central IDPMC6045814
Grant ListR01 HL126509 / HL / NHLBI NIH HHS / United States
R01 HL135007 / HL / NHLBI NIH HHS / United States
R01 GM114141 / GM / NIGMS NIH HHS / United States
R01 HL127640 / HL / NHLBI NIH HHS / United States
R01 HL112618 / HL / NHLBI NIH HHS / United States
R01 HL128331 / HL / NHLBI NIH HHS / United States
R01 HD089275 / HD / NICHD NIH HHS / United States