Evaluation of the effect of boron derivatives on cardiac differentiation of mouse pluripotent stem cells |
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| Affiliation: | 1. Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey;2. Current affiliation: Translational Stem Cell Biology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States;1. Department of Obstetrics and Gynaecology, Faculty of Veterinary Medicine, Istanbul University-Cerrahpaşa, Avcılar, Istanbul, Türkiye;2. Department of Internal Medicine, Faculty of Veterinary Medicine, Istanbul University-Cerrahpaşa, Avcılar, Istanbul, Türkiye;3. Department of Biophysics, Faculty of Medicine, Beykent University, Büyükçekmece, Istanbul, Türkiye;4. Department of Biophysics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Fatih, Istanbul, Türkiye;5. Department of Pathology, Faculty of Veterinary Medicine, Istanbul University-Cerrahpaşa, Büyükçemece, Istanbul, Türkiye;6. Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Türkiye;1. Center Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510120, Guangdong, China;2. State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510182, Guangdong, China;1. Department of Epidemiology, School of Public Health, Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, China;2. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;1. Departamento de Medicina, Universidade Federal de Sergipe (UFS), Campus da Saúde Prof. João Cardoso Do Nascimento Júnior, CCBS, Rua Cláudio Batista, s/n, Aracaju, Sergipe, Brazil;2. São Lucas Hospital – Rede D′OR (HSL), EMTN, Avenida Coronel Stanley da Silveira s/n, Aracaju, Sergipe, Brazil;3. Pós Graduação em Enfermagem, Universidade Federal de Pelotas (UFPel), Rua Gomes Carneiro, 01 / 2º andar – Sala 208, Pelotas, Rio Grande do Sul, Brazil;4. Departamento de Nutrição, Universidade Federal da Bahia, (UFBA), Rua Araújo Pinho 32, Canela, Salvador, Bahia, Brazil;5. Escola de Medicina, Universidade Federal de Uberlândia (UFU), Avenida Pará, bloco 2u, Uberlândia, Minas Gerais 1720, Brazil;1. Selçuk University, Medical Faculty, Departments Physiology and Histology and Embriyology, Konya, Turkey;2. Kirikkale University, Medical Faculty, Departments of Physiology, Kirikkale, Turkey |
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| Abstract: | BackgroundThe heart is one of the first organs to form during embryonic development and has a very important place. So much that the formation of a functional heart is completed on the 55th day of human development and the 15th day of mouse development. Myocardial, endocardial and epicardial cells, which are derived from the mesoderm layer, are the cells that form the basis of the heart. Cardiac development, like other embryonic developments, is tightly controlled and regulated by various signaling pathways. The WNT signaling pathway is the most studied of these signaling pathways and the one with the clearest relationship with heart development. It is known that boron compounds and the Wnt/β-catenin pathway are highly correlated. Therefore, this study aimed to investigate the role of boron compounds in heart development as well as its effect on pluripotency of mouse embryonic stem cells for the first time in the literature.MethodsToxicity of boron compounds was evaluated by using MTS analysis and obtained results were supported by morphological pictures, Trypan Blue staining and Annexin V staining. Additionally, the possible boron-related change in pluripotency of embryonic stem cells were analyzed with alkaline phosphatase activity and immunocytochemical staining of Oct4 protein as well as gene expression levels of pluripotency related OCT4, SOX2 and KLF4 genes. The alterations in the embryonic body formation capacity of mouse embryonic stem cells due to the application boron derivatives were also evaluated. Three linage differentiation was conducted to clarify the real impact of boron compounds on embryonic development. Lastly, cardiac differentiation of mESCs was investigated by using morphological pictures, cytosolic calcium measurement, gene expression and immunocytochemical analysis of cardiac differentiation related genes and in the presence of boron compounds.ResultsObtained results show that boron treatment maintains the pluripotency of embryonic stem cells at non-toxic concentrations. Additionally, endodermal, and mesodermal fate was found to be triggered after boron treatment. Also, initiation of cardiomyocyte differentiation by boron derivative treatments caused an increased gene expression levels of cardiac differentiation related TNNT2, Nkx2.5 and ISL-1 gene expression levels.ConclusionThis study indicates that boron application, which is responsible for maintaining pluripotency of mESCs, can be used for increased cardiomyocyte differentiation of mESCs. |
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| Keywords: | Boron Boric Acid Sodium Pentaborate Pentahydrate Mouse Pluripotent Stem cells Cardiac Differentiation |
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