title: Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules.
abstract: Astrocytes, due to the proximity to neuronal lineage and capability to proliferate, are ideal starting cells to regenerate neurons. Human fetal astrocytes have been successfully converted into neuronal cells by small molecules, which offered a broader range of further applications than transcription factor-mediated neuronal reprogramming. Here we report that human adult astrocytes could also be converted into neuronal cells by a different set of small molecules. These induced cells exhibited typical neuronal morphologies, expressed neuronal markers, and displayed neuronal electrophysiological properties. Genome-wide RNA-sequencing analysis showed that the global gene expression profile of induced neuronal cells resembled that of human embryonic stem cell-differentiated neurons. When transplanted into post-natal mouse brains, these induced neuronal cells could survive and become electrophysiologically mature. Altogether, our study provides a strategy to directly generate transgene-free neuronal cells from human adult astrocytes by small molecules.
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Wuqiang
authors.initials: W
authors.lastname: Guan
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Huihan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Binlong
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Ping
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
authors.forename: Xiuwu
authors.initials: X
authors.lastname: Bian
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: li_shen@zju.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: gpei@sibs.ac.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
mesh_terms: D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D054338:Cell Transdifferentiation / Q000187:drug effects*; D065150:Cellular Reprogramming / Q000187:drug effects* / Q000235:genetics; D016000:Cluster Analysis; D055724:Electrophysiological Phenomena; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D015415:Biomarkers
keywords: human adult astrocytes; neuronal cells; small molecules; transdifferentiation