Abstract
The introduction of genes associated with the fate of dopaminergic (DA) neurons may help to facilitate the differentiation of embryonic stem cells (ESC) to DA neurons. Here we used lentiviral vectors to drive lmx1b, a key transcription factor of dopaminergic neurons development, expression in ESC. Tyrosine hydroxylase-positive neurons were increased from 18% to nearly 50% when exogenous lmx1b was transduced. The enhanced Pitx3, Girk2, Nurr1 and DAT suggested that the increased differentiated neurons were mature A9 DA neurons. The results of [3H]dopamine reuptake assay indicated these differentiated neurons were all functional. Our study demonstrated that lmx1b was capable of promoting the differentiation of ESC to DA neurons.
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Acknowledgments
We are grateful to Pro. Naihe Jing in Shanghai institutes of Biological Sciences for his kind help in R1 neural differentiation. This work was funded by the National Program of Basic Research (2007CB947900, 2010CB945200, 2011CB504104) of China, the Natural Science Fund (30700888, 30770732, 30872729, 30971031), Key Discipline Program of Shanghai Municipality (S30202), Shanghai Key Project of Basic Science Research (10411954500), and Program for Outstanding Medical Academic Leader of Shanghai (LJ 06003).
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Each author has no conflicts of interest or financial interest.
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Tian, LP., Zhang, S., Zhang, YJ. et al. Lmx1b can promote the differentiation of embryonic stem cells to dopaminergic neurons associated with Parkinson’s disease. Biotechnol Lett 34, 1167–1174 (2012). https://doi.org/10.1007/s10529-012-0888-5
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DOI: https://doi.org/10.1007/s10529-012-0888-5