Characterization of Induced Pluripotent Stem Cell-derived Human Serotonergic Neurons.

Characterization of Induced Pluripotent Stem Cell-derived Human Serotonergic Neurons.
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DOI:
10.3389/fncel.2017.00131
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发表时间:
2017
影响因子:
5.3
通讯作者:
Lu J
Lu J
中科院分区:
医学2区
文献类型:
--
作者:
Cao L;Hu R;Xu T;Zhang ZN;Li W;Lu J

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在脑中,位于中缝核的多巴胺能神经元是神经递质5-羟色胺的唯一来源,其在脑发育和功能调节中起着关键作用。血清素系统功能障碍存在于许多精神疾病中。缺乏体外功能性人体模型限制了对人类中枢神经系统及其相关疾病的认识和临床应用。以前,我们已经开发了一种从诱导多能干细胞(iPSC)产生人肾上腺素能神经元的方法。在这项研究中,我们分析了这些人iPSC衍生的多巴胺能神经元在体外和体内的特点。我们在体外实验中发现这些人肾上腺素能神经元对选择性神经毒素5,7-二羟色胺(5,7-DHT)敏感。移植到新生小鼠体内后,细胞不仅表达其典型的分子标记,而且还表现出向宿主小脑、后脑和脊髓的迁移和投射。结果表明,这些人iPSC源性神经元具有脑内5-羟色胺能神经元的典型特征,为研究人5-羟色胺系统及其相关疾病提供了坚实的基础。
In the brain, the serotonergic neurons located in the raphe nucleus are the unique resource of the neurotransmitter serotonin, which plays a pivotal role in the regulation of brain development and functions. Dysfunction of the serotonin system is present in many psychiatric disorders. Lack of in vitro functional human model limits the understanding of human central serotonergic system and its related diseases and clinical applications. Previously, we have developed a method generating human serotonergic neurons from induced pluripotent stem cells (iPSCs). In this study, we analyzed the features of these human iPSCs-derived serotonergic neurons both in vitro and in vivo. We found that these human serotonergic neurons are sensitive to the selective neurotoxin 5, 7-Dihydroxytryptamine (5,7-DHT) in vitro. After being transplanted into newborn mice, the cells not only expressed their typical molecular markers, but also showed the migration and projection to the host’s cerebellum, hindbrain and spinal cord. The data demonstrate that these human iPSCs-derived neurons exhibit the typical features as the serotonergic neurons in the brain, which provides a solid foundation for studying on human serotonin system and its related disorders.
DOI: 10.1258/ebm.2010.009307
发表时间: 2010-05
期刊: Experimental biology and medicine (Maywood, N.J.)
影响因子: --
作者:
Tokuyama Y;Ingram SL;Woodward JS;Bethea CL
通讯作者: Bethea CL