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 S Bassel-Duby, Eric N Olson

Research output: Contribution to journalArticle

111 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1599-1603
Number of pages5
JournalScience
Volume338
Issue number6114
DOIs
StatePublished - Dec 21 2012

ASJC Scopus subject areas

  • General

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    Huang, G. N., Thatcher, J. E., McAnally, J., Kong, Y., Qi, X., Tan, W., DiMaio, J. M., Amatruda, J. F., Gerard, R. D., Hill, J. A., Bassel-Duby, R. S., & Olson, E. N. (2012). C/EBP transcription factors mediate epicardial activation during heart development and injury. Science, 338(6114), 1599-1603. https://doi.org/10.1126/science.1229765