Development and validation of an in vitro model system to study peripheral sensory neuron development and injury
Development and validation of an in vitro model system to study peripheral sensory neuron development and injury
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DOI：
10.1038/s41598-018-34280-3
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发表时间：
2018-10-29
影响因子：
4.6
通讯作者：
Carlsson, Leif
中科院分区：
文献类型：
--
作者：
Jones, Iwan;Yelhekar, Tushar Devanand;Carlsson, Leif
区分不同类型感觉的能力是由不同群体的外周感觉神经元调节的。人类外周感觉神经元无法进行研究，相关模型系统的可用性阻碍了研究其发育和疾病的努力。因此，从人类胚胎干细胞体外分化外周感觉神经元提供了一个有吸引力的替代方案，因为可以为专门研究发育和损伤的研究产生无限的生物材料来源。这项研究中提出的工作描述了使用小分子抑制剂从人类胚胎干细胞衍生出外周感觉神经元。分化的神经元表达规范和形态特异性的外周感觉神经元标记物，其亚群表现出人类伤害性神经元的功能特性，包括河豚毒素抗性钠电流和重复动作电位。此外，来源的细胞与人类供体雪旺细胞结合，可作为研究周围神经损伤后神经元死亡的分子机制的模型系统。从人类胚胎干细胞中快速高效地获得遗传多样性的外周感觉神经元，为这些特殊类型的细胞提供了无限的途径，并为未来的研究提供了一个宝贵的体外模型系统。
The ability to discriminate between diverse types of sensation is mediated by heterogeneous populations of peripheral sensory neurons. Human peripheral sensory neurons are inaccessible for research and efforts to study their development and disease have been hampered by the availability of relevant model systems. The in vitro differentiation of peripheral sensory neurons from human embryonic stem cells therefore provides an attractive alternative since an unlimited source of biological material can be generated for studies that specifically address development and injury. The work presented in this study describes the derivation of peripheral sensory neurons from human embryonic stem cells using small molecule inhibitors. The differentiated neurons express canonical- and modality-specific peripheral sensory neuron markers with subsets exhibiting functional properties of human nociceptive neurons that include tetrodotoxin-resistant sodium currents and repetitive action potentials. Moreover, the derived cells associate with human donor Schwann cells and can be used as a model system to investigate the molecular mechanisms underlying neuronal death following peripheral nerve injury. The quick and efficient derivation of genetically diverse peripheral sensory neurons from human embryonic stem cells offers unlimited access to these specialised cell types and provides an invaluable in vitro model system for future studies.