Abstract
Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes. In vivo dopaminergic neuron reprogramming by EMF stimulation of AuNPs efficiently and non-invasively alleviated symptoms in mouse Parkinson's disease models. This study provides a proof of principle for EMF-based in vivo lineage conversion as a potentially viable and safe therapeutic strategy for the treatment of neurodegenerative disorders.
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Acknowledgements
This work was supported by the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (NRF-2017M3A9C6029306, 2016R1A2B2014195, 2013M3A9B4076483, NRF-2015 M3A9B4051064), Korea Health Technology R&D Project, Ministry of Health & Welfare (HI16C1176), the Next-Generation BioGreen 21 Program, Rural Development Administration (PJ011077) and the Ministry of Food and Drug Safety in 2017 (14172MFDS974).
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J.Y., Y.K. and J.K. designed the study. J.Y., E.L., H.Y.K., D.Y., J.J., H.K., Y.C., W.L., J.S., S.B., W.Jang, W.Jun, S.K., J.H. and H.P. performed the experiments. J.Y., J.K. and C.J.L. analysed the data. Y.K., E.L., H.Y.K., D.Y. and S.H.M. contributed materials and/or analysis tools. The manuscript was written based on contributions by all the authors. All the authors approved the final version of the manuscript.
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Yoo, J., Lee, E., Kim, H. et al. Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson's disease therapy. Nature Nanotech 12, 1006–1014 (2017). https://doi.org/10.1038/nnano.2017.133
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DOI: https://doi.org/10.1038/nnano.2017.133
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