Phenotypic and Functional Characterization of Peripheral Sensory Neurons derived from Human Embryonic Stem Cells.

Phenotypic and Functional Characterization of Peripheral Sensory Neurons derived from Human Embryonic Stem Cells.
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DOI:
10.1038/s41598-017-19093-0
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发表时间:
2018-01-12
期刊:
影响因子:
4.6
通讯作者:
Dottori M
Dottori M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alshawaf AJ;Viventi S;Qiu W;D'Abaco G;Nayagam B;Erlichster M;Chana G;Everall I;Ivanusic J;Skafidas E;Dottori M

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背根神经节(DRG)由多种感觉神经元亚型组成,其功能是将感觉刺激(包括温度、压力、疼痛和位置)传递到中枢神经系统。我们对DRG感觉神经元的了解主要来自动物研究,而对人类DRG的了解则少得多。人类胚胎干细胞(hESC)是帮助缩小这一差距的宝贵资源。我们以前的研究报告了一个有效的系统,从人胚胎干细胞的神经嵴和DRG感觉神经元。在这里,我们表明,这种分化系统引起的感觉神经元亚型的异质性群体所表现出的表型和功能分析。此外,使用微电极阵列,在培养8周内监测hESC衍生的感觉神经元培养物的成熟速率,显示它们的自发放电活动在分化后约12天开始,并在约6周时达到最大放电。这些研究对于开发体外平台以研究在人类DRG内发现的感觉神经元亚型的多样性具有高度价值。
The dorsal root ganglia (DRG) consist of a multitude of sensory neuronal subtypes that function to relay sensory stimuli, including temperature, pressure, pain and position to the central nervous system. Our knowledge of DRG sensory neurons have been predominantly driven by animal studies and considerably less is known about the human DRG. Human embryonic stem cells (hESC) are valuable resource to help close this gap. Our previous studies reported an efficient system for deriving neural crest and DRG sensory neurons from hESC. Here we show that this differentiation system gives rise to heterogeneous populations of sensory neuronal subtypes as demonstrated by phenotypic and functional analyses. Furthermore, using microelectrode arrays the maturation rate of the hESC-derived sensory neuronal cultures was monitored over 8 weeks in culture, showing their spontaneous firing activities starting at about 12 days post-differentiation and reaching maximum firing at about 6 weeks. These studies are highly valuable for developing an in vitro platform to study the diversity of sensory neuronal subtypes found within the human DRG.
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