C/EBP Transcription Factors Mediate Epicardial Activation During Heart Development and Injury

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (Impact Factor: 33.61). 12/2012; 338(6114):1599-1603. DOI: 10.1126/science.1229765


The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential
for cardiac development and repair. Injury of the adult heart results in reactivation of a developmental gene program in the
epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic
heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during
heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered
on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced
injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial
activation and heart injury, providing a platform for enhancing cardiac regeneration.

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Available from: Robert D Gerard, Jun 23, 2014
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