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


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.

SUBMITTER: Huang GN 

PROVIDER: S-EPMC3613149 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Huang Guo N GN   Thatcher Jeffrey E JE   McAnally John J   Kong Yongli Y   Qi Xiaoxia X   Tan Wei W   DiMaio J Michael JM   Amatruda James F JF   Gerard Robert D RD   Hill Joseph A JA   Bassel-Duby Rhonda R   Olson Eric N EN  

Science (New York, N.Y.) 20121115 6114


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  ...[more]

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