Direct conversion of human fibroblasts to induced serotonergic neurons.
Direct conversion of human fibroblasts to induced serotonergic neurons.
复制标题
将人类成纤维细胞直接转化为诱导的血清素能神经元。
DOI：
10.1038/mp.2015.101
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发表时间：
2016-01
影响因子：
11
通讯作者：
Feng J
中科院分区：
文献类型：
--
作者：
Xu Z;Jiang H;Zhong P;Yan Z;Chen S;Feng J
5-羟色胺（5-HT）能神经元在脑中发挥多种广泛的功能。多巴胺能系统的功能障碍引起各种精神疾病，包括抑郁症、焦虑症、强迫症、自闭症和饮食失调。在这里，我们表明，人原代成纤维细胞直接转化为诱导的β-羟色胺（i5 HT）神经元的表达Ascl 1，Foxa 2，Lmx 1b和FEV。p53基因敲低和适当的培养条件包括缺氧可促进转分化。i5 HT神经元表达成熟多巴胺能神经元的标记物，具有Ca 2+依赖性5 HT释放和选择性5 HT摄取，表现出自发性动作电位和自发性兴奋性突触后电流。应用5-羟色胺显著增加自发动作电位的放电率，证明了15-HT神经元用于研究多巴胺能神经传递的功能效用。人类i5 HT神经元的可用性将对许多与神经元相关的精神疾病的研究和药物发现非常有用。
Serotonergic (5HT) neurons exert diverse and widespread functions in the brain. Dysfunction of the serotonergic system gives rise to a variety of mental illnesses including depression, anxiety, obsessive compulsive disorder, autism and eating disorders. Here we show that human primary fibroblasts were directly converted to induced serotonergic (i5HT) neurons by the expression of Ascl1, Foxa2, Lmx1b and FEV. The transdifferentiation was enhanced by p53 knockdown and appropriate culture conditions including hypoxia. The i5HT neurons expressed markers for mature serotonergic neurons, had Ca2+-dependent 5HT release and selective 5HT uptake, exhibited spontaneous action potentials and spontaneous excitatory postsynaptic currents. Application of serotonin significantly increased the firing rate of spontaneous action potentials, demonstrating the functional utility of i5HT neurons for studying serotonergic neurotransmission. The availability of human i5HT neurons will be very useful for research and drug discovery on many serotonin-related mental disorders.