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Frontiers in Biology

Front. Biol.    2015, Vol. 10 Issue (1) : 11-27
An epigenetic perspective on the failing heart and pluripotent-derived-cardiomyocytes for cell replacement therapy
Joshua D. TOMPKINS(),Arthur D. RIGGS
Department of Diabetes and Metabolic Disease Research, Beckman Research Institute/City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA 91010, USA
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As life expectancy rises, the prevalence of heart failure is steadily increasing, while donors for organ transplantation remain in short supply (Zwi-Dantsis and Gepstein, 2012). Indeed, myocardial infarction represents the foremost cause of death within industrialized nations (Henning, 2011) and further, approximately 1% of all newborns harbor a congenital heart defect. Although medical interventions allow>80% of those with cardiac defects to survive to adulthood, there are often extreme emotional and financial burdens that accompany such congenital anomalies, and many individuals will remain at a heightened risk for myocardial infarction throughout the remainder of their lives (Verheugt et al., 2010; Amianto et al., 2011). In this review, we will discuss the nature of the failing heart and strategies for repair from an epigenetic standpoint. Significant focus will reside on pluripotent-to-cardiomyocyte differentiation for cell replacement, epigenetic mechanisms of cardiomyocyte differentiation, epigenetic “memories,” and epigenetic control of cardiomyocyte cell fate toward translational utility.

Keywords heart failure      pluripotent      cardiomyocytes      epigenetics      DNA methylation      lncRNA     
Corresponding Author(s): Joshua D. TOMPKINS   
Just Accepted Date: 17 November 2014   Online First Date: 02 February 2015    Issue Date: 14 February 2015
 Cite this article:   
Joshua D. TOMPKINS,Arthur D. RIGGS. An epigenetic perspective on the failing heart and pluripotent-derived-cardiomyocytes for cell replacement therapy[J]. Front. Biol., 2015, 10(1): 11-27.
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Arthur D. RIGGS
Term Abbreviation
heart failure HF
myocardial infarction MI
cardiomyocyte CM
cardiac progenitor CP
ventricular cardiomyocyte VM
pluripotent-derived-cardiomyocyte pluripotent-CM
hESC-derived-cardiomyocyte hESC-CM
chromatin remodeling complex CRC
polycomb remodeling complex 2 PRC2
histone methyl transferase HMT
histone deacetylase HDAC
histone acetyltransferase HAT
X-chromosome inactivation XCI
non-coding RNA ncRNA
microRNA miRNA
long non-coding RNA lncRNA
Tab.1  Common abbreviations within article
Fig.1  Basic epigenetic mechanisms that govern chromatin accessibility and transcription activity. As shown, patterns of histone modifications, DNA methylation, ncRNA expression, and chromatin remodeling (including local nucleosome density) all can influence levels of chromatin compaction and ultimately transcription at a typical promoter (Arya et al., 2010; Bannister and Kouzarides, 2011; Fisher and Fisher, 2011; Handy et al., 2011; Huang and Li, 2012; the ENCODE Project Consortium, 2012; Grote and Herrmann, 2013; Chen and Dent, 2014). Common enzymes that control the deposition or removal of epigenetic marks are displayed in red. Complexes that ncRNAs may associate with toward chromatin modulation are shown in blue. miRNA is displayed post-transcription, processing, and nuclear export.
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