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

95 Citations (Scopus)

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

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Heart Injuries
CCAAT-Enhancer-Binding Proteins
Pericardium
Transcription Factors
Developmental Genes
Gene Expression
Neutrophil Infiltration
Organ Culture Techniques
Regeneration
Stem Cells
Wounds and Injuries

ASJC Scopus subject areas

  • General

Cite this

Huang, G. N., Thatcher, J. E., McAnally, J., Kong, Y., Qi, X., Tan, W., ... 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

C/EBP transcription factors mediate epicardial activation during heart development and injury. / Huang, Guo N.; Thatcher, Jeffrey E.; McAnally, John; Kong, Yongli; Qi, Xiaoxia; Tan, Wei; DiMaio, J. Michael; Amatruda, James F; Gerard, Robert D.; Hill, Joseph A; Bassel-Duby, Rhonda S; Olson, Eric N.

In: Science, Vol. 338, No. 6114, 21.12.2012, p. 1599-1603.

Research output: Contribution to journalArticle

Huang, GN, Thatcher, JE, McAnally, J, Kong, Y, Qi, X, Tan, W, DiMaio, JM, Amatruda, JF, Gerard, RD, Hill, JA, Bassel-Duby, RS & Olson, EN 2012, 'C/EBP transcription factors mediate epicardial activation during heart development and injury', Science, vol. 338, no. 6114, pp. 1599-1603. https://doi.org/10.1126/science.1229765
Huang GN, Thatcher JE, McAnally J, Kong Y, Qi X, Tan W et al. C/EBP transcription factors mediate epicardial activation during heart development and injury. Science. 2012 Dec 21;338(6114):1599-1603. https://doi.org/10.1126/science.1229765
Huang, Guo N. ; Thatcher, Jeffrey E. ; McAnally, John ; Kong, Yongli ; Qi, Xiaoxia ; Tan, Wei ; DiMaio, J. Michael ; Amatruda, James F ; Gerard, Robert D. ; Hill, Joseph A ; Bassel-Duby, Rhonda S ; Olson, Eric N. / C/EBP transcription factors mediate epicardial activation during heart development and injury. In: Science. 2012 ; Vol. 338, No. 6114. pp. 1599-1603.
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