The Specification and Maturation of Nociceptive Neurons from Human Embryonic Stem Cells.
The Specification and Maturation of Nociceptive Neurons from Human Embryonic Stem Cells.
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DOI：
10.1038/srep16821
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发表时间：
2015-11-19
影响因子：
4.6
通讯作者：
Li XJ
中科院分区：
文献类型：
--
作者：
Boisvert EM;Engle SJ;Hallowell SE;Liu P;Wang ZW;Li XJ
痛觉神经元通过向中枢神经系统传递痛觉刺激，在痛觉中起着至关重要的作用。然而，由于缺乏人类伤害神经元的可及性，对伤害神经元生物学的研究一直受到阻碍。在这里，我们描述了一个系统，有效地引导人类胚胎干细胞进入伤害性神经元首先诱导这些细胞的神经谱系。随后在特定的时间点和浓度添加维甲酸和BMP4，产生大量的神经嵴祖细胞（AP2α+, P75+），并进一步分化为伤害神经元（TRKA+, Nav1.7+, P2X3+）。过表达Neurogenin 1 （Neurog1）促进神经元表达与感觉神经元相关的基因（Peripherin, TrkA），进一步成熟为TRPV1+伤害性神经元。重要的是，Neurog1的过度表达增加了这些神经元对辣椒素刺激的反应，这是成熟的功能性伤害性神经元的标志。综上所述，这项研究揭示了Neurog1在产生功能性人类伤害神经元中所起的重要作用。
Nociceptive neurons play an essential role in pain sensation by transmitting painful stimuli to the central nervous system. However, investigations of nociceptive neuron biology have been hampered by the lack of accessibility of human nociceptive neurons. Here, we describe a system for efficiently guiding human embryonic stem cells into nociceptive neurons by first inducing these cells to the neural lineage. Subsequent addition of retinoic acid and BMP4 at specific time points and concentrations yielded a high population of neural crest progenitor cells (AP2α+, P75+), which further differentiated into nociceptive neurons (TRKA+, Nav1.7+, P2X3+). The overexpression of Neurogenin 1 (Neurog1) promoted the neurons to express genes related to sensory neurons (Peripherin, TrkA) and to further mature into TRPV1+ nociceptive neurons. Importantly, the overexpression of Neurog1 increased the response of these neurons to capsaicin stimulation, a hallmark of mature functional nociceptive neurons. Taken together, this study reveals the important role that Neurog1 plays in generating functional human nociceptive neurons.