title: Anacardic acid and thyroid hormone enhance cardiomyocytes production from undifferentiated mouse ES cells along functionally distinct pathways.
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.
authors.affiliation: National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00143, Rome, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Re
authors.affiliation: Institute of Medical Pathology, Catholic University, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Nanni
authors.affiliation: National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00143, Rome, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Aiello
authors.affiliation: Institute of Medical Pathology, Catholic University, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Granata
authors.affiliation: National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00143, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Colussi
authors.affiliation: Department of Biosciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Campostrini
authors.affiliation: Division of Cardiovascular Epigenetics, Internal Medicine Clinic III, Goethe University Frankfurt, 60590, Frankfurt, Germany.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spallotta
authors.affiliation: National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00143, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mattiussi
authors.affiliation: Institute of Medical Pathology, Catholic University, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pantisano
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: D'Angelo
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Biroccio
authors.affiliation: Bolzano Center for Biomedicine (Affiliated Institute of the University of Lübeck), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy.|Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossini
authors.affiliation: Department of Biosciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Barbuti
authors.affiliation: Department of Biosciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: DiFrancesco
authors.affiliation: Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trimarchi
authors.affiliation: Institute of Medical Pathology, Catholic University, Rome, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.affiliation: Division of Cardiovascular Epigenetics, Internal Medicine Clinic III, Goethe University Frankfurt, 60590, Frankfurt, Germany. gaetano@em.uni-frankfurt.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
authors.affiliation: National Research Council (CNR), Institute of Cell Biology and Neurobiology, 00143, Rome, Italy. antonella.farsetti@cnr.it.|Internal Medicine Clinic III, Goethe University Frankfurt, Frankfurt, Germany. antonella.farsetti@cnr.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Farsetti
mesh_terms: D048729:Anacardic Acids / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D044127:Epigenesis, Genetic; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D048729:Anacardic Acids; D014284:Triiodothyronine; C088115:anacardic acid
keywords: Cardiomyocytes; Epigenetics; Lysine acetylation; Mesoderm; Mouse ES