Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells
Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells
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DOI：
10.1073/pnas.0902396106
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发表时间：
2009-05-05
影响因子：
11.1
通讯作者：
Ericson, Johan
中科院分区：
文献类型：
--
作者：
Friling, Stina;Andersson, Elisabet;Ericson, Johan
参与CNS发育的信号传导因子已被用于控制胚胎干细胞（ESC）向中脑多巴胺（mesDA）神经元的分化，但倾向于产生有限产量的所需细胞类型。在这里，我们表明，强制表达Lmx 1a，一种转录因子，在胚胎发育过程中作为mesDA神经元的决定因素，可以有效地促进小鼠和人类胚胎干细胞的mesDA神经元的产生。在允许的培养条件下，75%-95%的小鼠ESC衍生的神经元表达真正的mesDA神经元的分子和生理特性。与原代mesDA神经元类似，这些细胞整合并支配6-羟基多巴胺损伤的新生大鼠的纹状体。因此，通过Lmx 1a的强制表达来富集功能性mesDA神经元的产生可能在帕金森病的细胞替代疗法中具有未来的重要性。
Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons. Similar to primary mesDA neurons, these cells integrate and innervate the striatum of 6-hydroxy dopamine lesioned neonatal rats. Thus, the enriched generation of functional mesDA neurons by forced expression of Lmx1a may be of future importance in cell replacement therapy of Parkinson disease.