title: Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation.
abstract: 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.
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Kunshan
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Xinpei
authors.initials: X
authors.lastname: Gao
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Junbang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institute of Neurobiology, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, 200092, China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.|Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, 200092, China.
authors.forename: Siguang
authors.initials: S
authors.lastname: Li
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China. yi.eve.sun@gmail.com.|Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. yi.eve.sun@gmail.com.|Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, 200092, China. yi.eve.sun@gmail.com.
authors.forename: Yi E
authors.initials: YE
authors.lastname: Sun
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis; D055724:Electrophysiological Phenomena / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D055106:Genome-Wide Association Study; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D005810:Multigene Family / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome / Q000502:physiology*
chemical_list: D000943:Antigens, Differentiation
keywords: Biomarkers for neuronal maturation; Patch-Seq; Ubiquitination and mitochondrial function; WGCNA; hESC/hiPSC-derived neuron