Initiating Events in Direct Cardiomyocyte Reprogramming

Summary: 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 mecha...

Full description

Bibliographic Details
Main Authors: Kimberly Sauls, Todd M. Greco, Li Wang, Meng Zou, Michelle Villasmil, Li Qian, Ileana M. Cristea, Frank L. Conlon
Format: Article
Language:English
Published: Elsevier 2018-02-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718300792
Description
Summary:Summary: 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.
ISSN:2211-1247