Ionizing radiation impacts on cardiac differentiation of mouse embryonic stem cells

Little is known about the effects of ionizing radiation on the earliest stages of embryonic development although it is well recognized that ionizing radiation is a natural part of our environment and further exposure may occur due to medical applications. The current study addresses this issue using D3 mouse embryonic stem cells as a model system. Cells were irradiated with either X-rays or carbon ions representing sparsely and densely ionizing radiation and their effect on the differentiation of D3 cells into spontaneously contracting cardiomyocytes via embryoid body formation was measured. This study is the first to demonstrate that ionizing radiation impairs the formation of beating cardiomyocytes with carbon ions being more detrimental than X-rays. However, after prolonged culture time the number of beating embryoid bodies derived from carbon ion irradiated cells almost reached control levels indicating that the surviving cells are still capable to develop along the cardiac lineage albeit with considerable delay. Reduced embryoid body size, failure to downregulate pluripotency markers and impaired expression of cardiac markers were identified as the cause of compromised cardiomyocyte formation. Dysregulation of cardiac differentiation was accompanied by alterations in the expression of endodermal and ectodermal markers that were more severe after carbon ion irradiation than after exposure to X-rays. In conclusion, our data show that carbon ion particle irradiation profoundly affects differentiation and thus may pose a higher risk to the early embryo than X-rays.