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Endocrine. 2016 Sep;53(3):681-8. doi: 10.1007/s12020-015-0751-2. Epub 2015 Nov 7.

Anacardic acid and thyroid hormone enhance cardiomyocytes production from undifferentiated mouse ES cells along functionally distinct pathways.

Author information

1
National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00143, Rome, Italy.
2
Institute of Medical Pathology, Catholic University, Rome, Italy.
3
Department of Biosciences, Università degli Studi di Milano, Milan, Italy.
4
Division of Cardiovascular Epigenetics, Internal Medicine Clinic III, Goethe University Frankfurt, 60590, Frankfurt, Germany.
5
Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
6
Bolzano Center for Biomedicine (Affiliated Institute of the University of Lübeck), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy.
7
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
8
Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
9
Division of Cardiovascular Epigenetics, Internal Medicine Clinic III, Goethe University Frankfurt, 60590, Frankfurt, Germany. gaetano@em.uni-frankfurt.
10
National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00143, Rome, Italy. antonella.farsetti@cnr.it.
11
Internal Medicine Clinic III, Goethe University Frankfurt, Frankfurt, Germany. antonella.farsetti@cnr.it.

Abstract

The epigenetics of early commitment to embryonal cardiomyocyte is poorly understood. In this work, we compared the effect of thyroid hormone and that of anacardic acid, a naturally occurring histone acetylase inhibitor, or both in combination, on mouse embryonic stem cells (mES) differentiating into embryonal cardiomyocyte by embryoid bodies (EBs) formation. Although the results indicated that anacardic acid (AA) and thyroid hormone were both efficient in promoting cardiomyocyte differentiation, we noticed that a transient exposure of mES to AA alone was sufficient to enlarge the beating areas of EBs compared to those of untreated controls. This effect was associated with changes in the chromatin structure at the promoters of specific cardiomyogenic genes. Among them, a rapid induction of the transcription factor Castor 1 (CASZ1), important for cardiomyocytes differentiation and maturation during embryonic development, was observed in the presence of AA. In contrast, thyroid hormone (T 3) was more effective in stimulating spontaneous firing, thus suggesting a role in the production of a population of cardiomyocyte with pacemaker properties. In conclusion, AA and thyroid hormone both enhanced cardiomyocyte formation along in apparently distinct pathways.

KEYWORDS:

Cardiomyocytes; Epigenetics; Lysine acetylation; Mesoderm; Mouse ES

PMID:
26547215
DOI:
10.1007/s12020-015-0751-2
[Indexed for MEDLINE]

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