Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells
The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/4651238 |
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| author | Robin Duelen Guillaume Gilbert Abdulsamie Patel Nathalie de Schaetzen Liesbeth De Waele Llewelyn Roderick Karin R. Sipido Catherine M. Verfaillie Gunnar M. Buyse Lieven Thorrez Maurilio Sampaolesi |
| author_facet | Robin Duelen Guillaume Gilbert Abdulsamie Patel Nathalie de Schaetzen Liesbeth De Waele Llewelyn Roderick Karin R. Sipido Catherine M. Verfaillie Gunnar M. Buyse Lieven Thorrez Maurilio Sampaolesi |
| author_sort | Robin Duelen |
| collection | DOAJ |
| description | The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation. Moreover, a dose-dependent increase in the coreceptor expression of the TGF-β superfamily member CRIPTO-1 was observed in response to Activin A. We hypothesized that interactions between cells derived from meso- and endodermal lineages in embryoid bodies contributed to improved cell maturation in early stages of cardiac differentiation, improving the beating frequency and the percentage of contracting embryoid bodies. Activin A did not seem to affect the properties of cardiomyocytes at later stages of differentiation, measuring action potentials, and intracellular Ca2+ dynamics. These findings are relevant for improving our understanding on human heart development, and the proposed protocol could be further explored to obtain cardiomyocytes with functional phenotypes, similar to those observed in adult cardiac myocytes. |
| format | Article |
| id | doaj-art-ec180802ac9541a284ff1e0893a521e1 |
| institution | DOAJ |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-ec180802ac9541a284ff1e0893a521e12025-08-20T03:21:23ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/46512384651238Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem CellsRobin Duelen0Guillaume Gilbert1Abdulsamie Patel2Nathalie de Schaetzen3Liesbeth De Waele4Llewelyn Roderick5Karin R. Sipido6Catherine M. Verfaillie7Gunnar M. Buyse8Lieven Thorrez9Maurilio Sampaolesi10Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumExperimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, BelgiumStem Cell Institute Leuven and Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumChild Neurology, University Hospitals Leuven, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumExperimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, BelgiumExperimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, BelgiumStem Cell Institute Leuven and Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumChild Neurology, University Hospitals Leuven, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumTranslational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, BelgiumThe use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation. Moreover, a dose-dependent increase in the coreceptor expression of the TGF-β superfamily member CRIPTO-1 was observed in response to Activin A. We hypothesized that interactions between cells derived from meso- and endodermal lineages in embryoid bodies contributed to improved cell maturation in early stages of cardiac differentiation, improving the beating frequency and the percentage of contracting embryoid bodies. Activin A did not seem to affect the properties of cardiomyocytes at later stages of differentiation, measuring action potentials, and intracellular Ca2+ dynamics. These findings are relevant for improving our understanding on human heart development, and the proposed protocol could be further explored to obtain cardiomyocytes with functional phenotypes, similar to those observed in adult cardiac myocytes.http://dx.doi.org/10.1155/2017/4651238 |
| spellingShingle | Robin Duelen Guillaume Gilbert Abdulsamie Patel Nathalie de Schaetzen Liesbeth De Waele Llewelyn Roderick Karin R. Sipido Catherine M. Verfaillie Gunnar M. Buyse Lieven Thorrez Maurilio Sampaolesi Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells Stem Cells International |
| title | Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells |
| title_full | Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells |
| title_fullStr | Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells |
| title_full_unstemmed | Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells |
| title_short | Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells |
| title_sort | activin a modulates cripto 1 hnf4α cells to guide cardiac differentiation from human embryonic stem cells |
| url | http://dx.doi.org/10.1155/2017/4651238 |
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