Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation.
Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation.
复制标题
耦合电生理记录和单细胞转录组分析揭示了神经元成熟的分子机制
DOI：
10.1007/s13238-016-0247-8
复制
发表时间：
2016-03
期刊：
影响因子：
21.1
通讯作者：
Sun YE
中科院分区：
文献类型：
--
作者：
Chen X;Zhang K;Zhou L;Gao X;Wang J;Yao Y;He F;Luo Y;Yu Y;Li S;Cheng L;Sun YE
哺乳动物的大脑是异质的，包含数十亿个神经元和数万亿个突触，形成各种神经回路，通过这些神经回路产生感觉、运动、思想和情感。大脑细胞的异质性使得研究神经回路的连接、修剪、激活和可塑性的分子逻辑变得困难，直到最近，单细胞分辨率的转录组分析使得解码上述电路特性背后的基因调控网络成为可能。在这里，我们报告成功地执行电生理和全基因组转录组分析单个人类神经元在培养。利用加权基因共表达网络分析（WGCNA），我们通过电生理特征识别出与神经元成熟高度相关的基因簇。揭示了神经元成熟与泛素化和线粒体功能相关基因之间的紧密联系。此外，我们还确定了一系列候选基因，这些基因可能作为神经元成熟的生物标志物。耦合电生理记录和单细胞转录组分析将成为未来揭示神经回路功能分子逻辑的有力工具。
The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA), we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.