Differentiation of embryonic stem cell-derived dopaminergic neurons is enhanced by survival-promoting factors

被引:102
作者
Rolletschek, A
Chang, H
Guan, KM
Czyz, J
Meyer, M
Wobus, AM [1 ]
机构
[1] Inst Plant Genet & Crop Plant Res, In Vitro Differentiat Grp, D-06466 Gatersleben, Germany
[2] Univ So Denmark, Med Biol Inst, DK-5000 Odense C, Denmark
关键词
embryonic stem cell differentiation; dopaminergic neuron; tyrosine hydroxylase; Nurr1; interleukin-1 beta glial cell line-derived neurotrophic factor;
D O I
10.1016/S0925-4773(01)00385-9
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Here, we describe the generation of viable and dopamin-producing neurons derived from pluripotent mouse embryonic stem cells. Neurotrophic factors in combination with survival-promoting factors, such as interleukin-1 beta, glial cell line-derived neurotrophic factor, neurturin, transforming growth factor-beta (3) and dibutyryl-cyclic AMP, significantly enhanced Nurr1 and tyrosine hydroxylase (TH) mRNA levels, whereas En-1, mash-1 and dopamine-2-receptor mRNA levels were not upregulated. In parallel, mRNA levels of the anti-apoptotic gene bcl-2 were found to be upregulated at terminal stages. Double immunofluorescence analysis revealed increased numbers of TH- and dopamine transporter-, but not gamma -aminobutyric acid- and serotonin-positive neurons in relation to synaptophysin-labeled cells by survival-promoting factors. Moreover, high-performance liquid chromatography analysis showed detectable levels of intracellular dopamine. We conclude that survival-promoting factors enhance differentiation, survival and maintenance of dopaminergic neurons derived from embryonic stem cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:93 / 104
页数:12
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