Functional characterization of rhesus embryonic stem cell-derived serotonin neurons.
Functional characterization of rhesus embryonic stem cell-derived serotonin neurons.
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DOI：
10.1258/ebm.2010.009307
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Bethea CL
中科院分区：
文献类型：
--
作者：
Tokuyama Y;Ingram SL;Woodward JS;Bethea CL
5-羟色胺系统的最佳功能对心理健康至关重要，其在精神病理学中的作用是无可争议的。提高在培养中研究灵长类5-羟色胺神经元的能力将有助于理解介导药物和其他影响人类心理健康的表观遗传或发育因素作用的细胞内信号传导途径。我们是第一个报告非人灵长类恒河猴胚胎干细胞（ESC）系366.4分化为5-羟色胺神经元培养物的小组。在这项研究中，我们优化产量，并获得衍生的5-羟色胺神经元的功能特性。在扩增阶段用FGF 4和SHH顺序处理ESC 366.4显著增加5-羟色胺神经元的产量。这些5-羟色胺神经元传播动作电位并表达GABA受体。我们还首次证明，这些ESC衍生的5-羟色胺神经元表现出功能性的高亲和力转运位点，以及高亲和力的5 HT 1A结合位点，这是常见的精神活性药物的基本目标。最后，为了测试这种方法的通用性，我们利用另一种恒河猴ESC系ORMES-22，其有效地分化为5-羟色胺神经元。总之，这些研究结果表明，我们的方案的可行性，指导不同的灵长类神经元ESC线的5-羟色胺神经元的生理特性，这使得他们在体外模型系统是一个有用的。
Optimal function of the serotonin system is essential for mental health and its role in psychopathologies is undisputed. Enhancing the ability to study primate serotonin neurons in culture would facilitate understanding of intracellular signaling pathways that mediate the action of drugs and other epigenetic or developmental factors impacting human mental health. We were the first group to report differentiation of the nonhuman primate rhesus monkey embryonic stem cells (ESC) line 366.4 into cultures of serotonin neurons. In this study, we optimized yield and obtained functional characteristics of the derived serotonin neurons. Sequential treatments of ESC 366.4 during expansion stage with FGF4 and SHH markedly increased the yield of serotonin neurons. These serotonin neurons propagated action potentials and expressed GABA receptors. Also for the first time we demonstrate that these ESC-derived serotonin neurons exhibit functional high affinity transporter sites, as well as high affinity 5HT1A binding sites, which are essential targets of common psychoactive drugs. Finally, to test the generality of this method, we utilized another rhesus ESC line, ORMES-22, which efficiently differentiated into serotonin neurons. Together these findings demonstrate the feasibility of our protocol to direct different primate neuronal ESC lines to serotonin neurons with physiological characteristics, which makes them a useful in vitro model system.
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影响因子：
7.4
作者：
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通讯作者：
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