2. Academic Validation
  3. Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules

Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules

  • Stem Cell Reports. 2017 Mar 14;8(3):538-547. doi: 10.1016/j.stemcr.2017.01.014.
Longfei Gao 1,  Wuqiang Guan 2,  Min Wang 2,  Huihan Wang 3,  Jiali Yu 3,  Qing Liu 4,  Binlong Qiu 1,  Yongchun Yu 2,  Yifang Ping 4,  Xiuwu Bian 4,  Li Shen 5,  Gang Pei 6
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • 4 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.
  • 5 Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: li_shen@zju.edu.cn.
  • 6 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.
PMID: 28216149 DOI: 10.1016/j.stemcr.2017.01.014
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.

Keywords

human adult astrocytes; neuronal cells; small molecules; transdifferentiation.

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