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C/EBP Transcription Factors Mediate Epicardial Activation During Heart Development and Injury
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Guo N. Huang, Jeffrey E. Thatcher, John McAnally, Yongli Kong, Xiaoxia Qi, Wei Tan, J. Michael DiMaio, James F. Amatruda, Robert D. Gerard, Joseph A. Hill, Rhonda Bassel-Duby, Eric N. Olson
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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. 8 C! l* t5 K& Q( w. G& f
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发表于 2012-11-20 11:27
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