Stem Cell Reports ( IF 5.9 ) Pub Date : 2021-02-04 , DOI: 10.1016/j.stemcr.2021.01.001
Kenyi Saito-Diaz 1 , Jonathan Roy Street 2 , Heidi Ulrichs 1 , Nadja Zeltner 3
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The three peripheral sensory neuron (SN) subtypes, nociceptors, mechanoreceptors, and proprioceptors, localize to dorsal root ganglia and convey sensations such as pain, temperature, pressure, and limb movement/position. Despite previous reports, to date no protocol is available allowing the generation of all three SN subtypes at high efficiency and purity from human pluripotent stem cells (hPSCs). We describe a chemically defined differentiation protocol that generates all three SN subtypes from the same starting population, as well as methods to enrich for each individual subtype. The protocol yields high efficiency and purity cultures that are electrically active and respond to specific stimuli. We describe their molecular character and maturity stage and provide evidence for their use as an axotomy model; we show disease phenotypes in hPSCs derived from patients with familial dysautonomia. Our protocol will allow the modeling of human disorders affecting SNs, the search for treatments, and the study of human development.
中文翻译:
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从人类多能干细胞的同一培养物中衍生外周痛觉、机械感受和本体感觉神经元
三种外周感觉神经元 (SN) 亚型、伤害感受器、机械感受器和本体感受器定位于背根神经节并传递诸如疼痛、温度、压力和肢体运动/位置等感觉。尽管有先前的报道,但迄今为止还没有任何协议允许从人类多能干细胞 (hPSC) 中以高效率和纯度生成所有三种 SN 亚型。我们描述了一种化学定义的分化协议,该协议从相同的起始群体中生成所有三种 SN 亚型,以及丰富每个个体亚型的方法。该协议产生具有电活性并对特定刺激作出反应的高效率和纯度培养物。我们描述了它们的分子特征和成熟阶段,并提供了将它们用作轴突模型的证据;我们展示了来自家族性自主神经功能障碍患者的 hPSC 中的疾病表型。我们的协议将允许对影响 SN 的人类疾病进行建模、寻找治疗方法以及研究人类发展。