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Kv7 通道在纹状体神经元发育过程中上调,并促进人诱导多能干细胞衍生神经元的成熟。

Kv7 channels are upregulated during striatal neuron development and promote maturation of human iPSC-derived neurons.

机构信息

School of Dental Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK.

School of Biosciences, Cardiff University, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, UK.

出版信息

Pflugers Arch. 2018 Sep;470(9):1359-1376. doi: 10.1007/s00424-018-2155-7. Epub 2018 May 24.

Abstract

Kv7 channels determine the resting membrane potential of neurons and regulate their excitability. Even though dysfunction of Kv7 channels has been linked to several debilitating childhood neuronal disorders, the ontogeny of the constituent genes, which encode Kv7 channels (KNCQ), and expression of their subunits have been largely unexplored. Here, we show that developmentally regulated expression of specific KCNQ mRNA and Kv7 channel subunits in mouse and human striatum is crucial to the functional maturation of mouse striatal neurons and human-induced pluripotent stem cell-derived neurons. This demonstrates their pivotal role in normal development and maturation, the knowledge of which can now be harnessed to synchronise and accelerate neuronal differentiation of stem cell-derived neurons, enhancing their utility for disease modelling and drug discovery.

摘要

Kv7 通道决定神经元的静息膜电位,并调节其兴奋性。尽管 Kv7 通道功能障碍与几种使人衰弱的儿童期神经元疾病有关,但构成 Kv7 通道(KNCQ)的基因的个体发生及其亚基的表达在很大程度上仍未得到探索。在这里,我们表明,在小鼠和人类纹状体中特定的 KCNQ mRNA 和 Kv7 通道亚基的发育调控表达对于小鼠纹状体神经元和人诱导多能干细胞衍生神经元的功能成熟至关重要。这表明它们在正常发育和成熟中起着关键作用,现在可以利用这些知识来同步和加速干细胞衍生神经元的分化,提高它们在疾病建模和药物发现中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/686b/6096767/87fcbc65860b/424_2018_2155_Fig1_HTML.jpg

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