西亚试剂：C/EBP Transcription Factors Mediate Epicardial Activation D

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

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

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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