Glutamatergic neuronal differentiation of mouse embryonic stem cells after transient expression of neurogenin 1 and treatment with BDNF and GDNF: in vitro and in vivo studies.
Glutamatergic neuronal differentiation of mouse embryonic stem cells after transient expression of neurogenin 1 and treatment with BDNF and GDNF: in vitro and in vivo studies.
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DOI：
10.1523/jneurosci.0563-08.2008
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发表时间：
2008-11-26
期刊：
影响因子：
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通讯作者：
Altschuler RA
中科院分区：
文献类型：
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作者：
Reyes JH;O'Shea KS;Wys NL;Velkey JM;Prieskorn DM;Wesolowski K;Miller JM;Altschuler RA
多能性神经上皮向神经元和胶质细胞的分化是由生长因子和细胞型限制性转录因子相互作用完成的。获得特定神经元表型的一种方法是在胚胎干细胞（ES）细胞中概括这些因子的表达。为了实现听觉神经替代的最终目标，当前研究的目的是从胚胎干细胞中产生听觉神经样谷氨酸能神经元。短暂表达Neurog1促进体外广泛的神经元分化；当补充BDNF和GDNF时，75%的ES细胞来源的神经元在体外5D后获得谷氨酸能表型。将小鼠胚胎干细胞置于豚鼠耳蜗中，诱导神经g1表达48小时，然后灌注BDNF/GDNF 26天。体内分化导致50-75%的胚胎干细胞具有早期神经元标记，这些细胞中的大多数具有谷氨酸能表型。这是第一个报道高百分比的胚胎干细胞分化为谷氨酸能表型的研究，并为听神经细胞替代奠定了基础。
Differentiation of the pluripotent neuroepithelium into neurons and glia is accomplished by the interaction of growth factors and cell-type restricted transcription factors. One approach to obtaining a particular neuronal phenotype is by recapitulating the expression of these factors in embryonic stem (ES) cells. Towards the eventual goal of auditory nerve replacement, the aim of the current investigation was to generate auditory nerve-like glutamatergic neurons from ES cells. Transient expression of Neurog1 promoted widespread neuronal differentiation in vitro; when supplemented with BDNF and GDNF, 75% of ES cell-derived neurons attained a glutamatergic phenotype after 5D in vitro. Mouse ES cells were also placed into deafened guinea pig cochleae and Neurog1 expression was induced for 48h followed by 26 days of BDNF/GDNF infusion. In vivo differentiation resulted in 50–75% of ES cells bearing markers of early neurons, and a majority of these cells had a glutamatergic phenotype. This is the first study to report a high percentage of ES cell differentiation into a glutamatergic phenotype and sets the stage for cell replacement of auditory nerve.