1. Developmental Biology
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Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4

  1. Jianlin Liang
  2. Nan Wang
  3. Jing He
  4. Jian Du
  5. Yahui Guo
  6. Lin Li
  7. Wenbo Wu
  8. Chencheng Yao
  9. Zheng Li
  10. Kehkooi Kee  Is a corresponding author
  1. Tsinghua University, China
  2. National Institute of Biological Sciences, China
  3. Shanghai Jiao Tong University School of Medicine, China
Research Article
  • Cited 8
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Cite this article as: eLife 2019;8:e48767 doi: 10.7554/eLife.48767

Abstract

Sertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). Here, we report the in vitro reprogramming of fibroblasts to human induced Sertoli-like cells (hiSCs). Initially, five transcriptional factors and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles and cellular properties that are similar to those of primary human Sertoli cells. Moreover, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. hiSCs suppress the proliferation of human T lymphocytes and protect xenotransplanted human cells in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli only syndrome (SCO), CX43, is indeed important in regulating the maturation of Sertoli cells.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated

Article and author information

Author details

  1. Jianlin Liang

    Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Nan Wang

    Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Jing He

    Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Jian Du

    Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yahui Guo

    Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Lin Li

    Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Wenbo Wu

    National Institute of Biological Sciences, Beijiing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Chencheng Yao

    Department of Andrology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Zheng Li

    Department of Andrology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Kehkooi Kee

    Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
    For correspondence
    kkee@tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6926-7203

Funding

Ministry of Science and Technology of the People's Republic of China (2017YFC1001601)

  • Kehkooi Kee

Ministry of Science and Technology of the People's Republic of China (2018YFA0107703)

  • Kehkooi Kee

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

Ethics

Animal experimentation: C57BL/6 mice were purchased from Vital River Laboratory Animal Technology Co., Ltd (Beijing, China). All animal maintenance and experimental procedures were performed according to the guidelines of the Institutional Animal Care and Use Committee (IACUC) of Tsinghua University, Beijing, China (Approval number: 17-JJK1).

Reviewing Editor

  1. William E Lowry, UCLA, United States

Publication history

  1. Received: May 24, 2019
  2. Accepted: November 9, 2019
  3. Accepted Manuscript published: November 11, 2019 (version 1)
  4. Version of Record published: November 27, 2019 (version 2)

Copyright

© 2019, Liang 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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