Induction of human Somatostatin and Parvalbumin neurons by expressing a single transcription factor LIM Homeobox 6

  1. Fang Yuan
  2. Xin Chen
  3. Kai-Heng Fang
  4. Yuanyuan Wang
  5. Mingyan Lin
  6. Shi-Bo Xu
  7. Hai-Qin Huo
  8. Min Xu
  9. Lixiang Ma
  10. Yuejun Chen
  11. Shuijin He  Is a corresponding author
  12. Yan Liu  Is a corresponding author
  1. Nanjing Medical University, China
  2. ShanghaiTech University, China
  3. Fudan University, China
  4. Chinese Academy of Sciences, China

Abstract

Human GABAergic interneurons (GIN) are implicated in normal brain function as well as numerous mental disorders. However, generation of functional human GIN subtypes from human pluripotent stem cells (hPSCs) has not been established. By expressing LHX6, a transcriptional factor critical for GIN development, we have induced hPSCs to GINs, including somatostatin (SST, 29%) and parvalbumin (PV, 21%) neurons. Our RNAseq results also confirmed alteration of GINs identity with the overexpression of LHX6. Five months after transplantation into the mouse brain, the human GABA precursors generated increased population of SST and PV neurons by overexpressing LHX6. Importantly, the grafted human GINs exhibited functional electrophysiological properties and even fast-spiking like action potentials. Thus, expression of the single transcription factor LHX6 under our GIN differentiation condition is sufficient to robustly induce human PV and SST subtypes.

Data availability

Sequencing data have been deposited in GEO under accession codesGSE114553. All data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Fang Yuan

    School of Pharmacy, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xin Chen

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Kai-Heng Fang

    School of Pharmacy, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuanyuan Wang

    Department of Neuroscience, School of Basic Medical Science, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Mingyan Lin

    Department of Neuroscience, School of Basic Medical Science, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Shi-Bo Xu

    School of Pharmacy, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Hai-Qin Huo

    School of Pharmacy, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Min Xu

    School of Pharmacy, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Lixiang Ma

    Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Yuejun Chen

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Shuijin He

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    For correspondence
    heshj@shanghaitech.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  12. Yan Liu

    School of Pharmacy, Nanjing Medical University, Nanjing, China
    For correspondence
    yanliu@njmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2918-5398

Funding

National Natural Science Foundation of China (81471301)

  • Yan Liu

National Key Research and Development Program of China (2016YFC1306703)

  • Yan Liu

Jiangsu Outstanding Young Investigator Program (BK20160044)

  • Yan Liu

ShanghaiTech Start-up Foundation

  • Shuijin He

Postgraduate Research and Practice Innovation Program of Jiangsu Province

  • Fang Yuan

Strategic Priority Research Program of the Chinese Academy of the Chinese Academy of Sciences (XDA16010306)

  • Yan Liu

National Natural Science Foundation of China (31671063)

  • Yan Liu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: SCID mice were purchased from the Model Animal Research Center of Nanjing University. All of the animal experiments followed standard experimental protocols and were approved by the Animal Care and Use Committee at Nanjing Medical University(IACUC-1601129).

Human subjects: H9 cell line was purchased from Wicell Agreeement (NO.16-W0060)For ips cell line, verbal and written consent was obtained from the person.The study was approved by the ethic community of Nanjing Medical University[(2017)NO.217].

Reviewing Editor

  1. Martin Pera, University of Melbourne, Australia

Publication history

  1. Received: April 10, 2018
  2. Accepted: September 24, 2018
  3. Accepted Manuscript published: September 25, 2018 (version 1)
  4. Version of Record published: October 11, 2018 (version 2)

Copyright

© 2018, Yuan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Fang Yuan
  2. Xin Chen
  3. Kai-Heng Fang
  4. Yuanyuan Wang
  5. Mingyan Lin
  6. Shi-Bo Xu
  7. Hai-Qin Huo
  8. Min Xu
  9. Lixiang Ma
  10. Yuejun Chen
  11. Shuijin He
  12. Yan Liu
(2018)
Induction of human Somatostatin and Parvalbumin neurons by expressing a single transcription factor LIM Homeobox 6
eLife 7:e37382.
https://doi.org/10.7554/eLife.37382

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