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Science. 2012 Dec 21;338(6114):1599-603. doi: 10.1126/science.1229765. Epub 2012 Nov 15.

C/EBP transcription factors mediate epicardial activation during heart development and injury.

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1
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

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.

PMID:
23160954
PMCID:
PMC3613149
DOI:
10.1126/science.1229765
[Indexed for MEDLINE]
Free PMC Article

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