Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation  

作　　者：Xiaoying Chen Kunshan Zhang Liqiang Zhou Xinpei Gao Junbang Wang Yinan Yao Fei He Yuping Luo Yongchun Yu Siguang Li Liming Cheng Yi E. Sun 

机构地区：[1]Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China [2]Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA [3]Institute of Neurobiology, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China [4]Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China

出　　处：《Protein & Cell》2016年第3期175-186,共12页蛋白质与细胞（英文版）

基　　金：The online version of this article （doi：10.1007/s13238-016-0247-8） contains supplementary material, which is available to authorized users.This work was supported by the National Basic Research Program （973 Program） （No. 2012CB966303）, the National Natural Science Foundation of China （Grant Nos. 81330030, 91319309, and 31271371）, the Science and Technology Department of Yunnan Province （Grant 2012HA013）, the Yunnan Basic Research Projects （Grant 2014FC004）, and the Doctoral Tutor of Education Department of Shanghai, China （Grant 20130072110021 ）, grants from NASAD： BRN ＆ BEHV RES FND 23072, NIH R21：IR21NS095184-01 and finally, a fellowship from China Scholarship Council to X. -Y.C.

摘　　要：The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming vari- ous 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 per- forming 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 neu- ronal 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.The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming vari- ous 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 per- forming 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 neu- ronal 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.

关 键 词：Patch-Seq hESC/hiPSC-derived neuron WGCNA Biomarkers for neuronal maturation Ubiquitination and mitochondrial function 

分 类 号：Q255[生物学—细胞生物学] TP18[自动化与计算机技术—控制理论与控制工程]