Cao Lining, Hu Rui, Xu Ting, Zhang Zhen-Ning, Li Weida, Lu Jianfeng
Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji UniversityShanghai, China.
Waisman Center, University of WisconsinMadison, WI, USA.
Front Cell Neurosci. 2017 May 8;11:131. doi: 10.3389/fncel.2017.00131. eCollection 2017.
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 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 and . We found that these human serotonergic neurons are sensitive to the selective neurotoxin 5, 7-Dihydroxytryptamine (5,7-DHT) . 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.
在大脑中，位于中缝核的血清素能神经元是神经递质血清素的唯一来源，血清素在大脑发育和功能调节中起关键作用。血清素系统功能障碍存在于许多精神疾病中。缺乏功能性人类模型限制了对人类中枢血清素能系统及其相关疾病的理解以及临床应用。此前，我们已开发出一种从诱导多能干细胞（iPSC）生成人类血清素能神经元的方法。在本研究中，我们分析了这些源自人类iPSC的血清素能神经元的特征。我们发现这些人类血清素能神经元对选择性神经毒素5,7-二羟基色胺（5,7-DHT）敏感。将这些细胞移植到新生小鼠体内后，它们不仅表达其典型的分子标记，还向宿主的小脑、后脑和脊髓迁移并形成投射。数据表明，这些源自人类iPSC的神经元表现出大脑中血清素能神经元的典型特征，这为研究人类血清素系统及其相关疾病提供了坚实基础。
