Young Gareth T, Gutteridge Alex, Fox Heather DE, Wilbrey Anna L, Cao Lishuang, Cho Lily T, Brown Adam R, Benn Caroline L, Kammonen Laura R, Friedman Julia H, Bictash Magda, Whiting Paul, Bilsland James G, Stevens Edward B
Pfizer Neusentis, Cambridge, UK.
Pfizer Neusentis, Cambridge, UK.
Mol Ther. 2014 Aug;22(8):1530-1543. doi: 10.1038/mt.2014.86. Epub 2014 May 15.
The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell-derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.
通过多能干细胞的定向分化产生人类感觉神经元为研究疼痛生物学带来了新机遇。此前无法生成这种细胞类型意味着,直到现在对它们的研究一直依赖于啮齿动物模型。在此,我们结合群体和单细胞技术,对源自人类胚胎干细胞的感觉神经元进行详细的分子、电生理和药理学表型分析。我们描述了定向分化6周内细胞群体的演变过程;这一过程产生了一个在很大程度上均一的神经元群体,其在分子和功能上与源自成熟背根神经节的人类感觉神经元相当。这项工作开启了利用多能干细胞衍生的感觉神经元研究人类神经元生理学以及作为疼痛和感觉障碍药物发现的体外模型的前景。