Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4
- Tsinghua University, China
- National Institute of Biological Sciences, China
- Shanghai Jiao Tong University School of Medicine, China
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.
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HiSC RNA sequence dataNCBI Gene Expression Omnibus, GSE133757.
Article and author information
Author details
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.
Reviewing Editor
- William E Lowry, UCLA, United States
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).
Version history
- Received: May 24, 2019
- Accepted: November 9, 2019
- Accepted Manuscript published: November 11, 2019 (version 1)
- 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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Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4
eLife 8:e48767.
https://doi.org/10.7554/eLife.48767
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