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Stem Cell Reports. 2018 Feb 13;10(2):509-523. doi: 10.1016/j.stemcr.2018.01.001. Epub 2018 Feb 1.

In Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells.

Author information

1
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
2
Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
3
Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
4
Department of Andrology, Urologic Medical Center, Shanghai Key Lab of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
5
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China; Department of Animal Science, Michigan State University, Lansing, MI 48824, USA. Electronic address: ywang@bio.ecnu.edu.cn.

Abstract

Due to differences across species, the mechanisms of cell fate decisions determined in mice cannot be readily extrapolated to humans. In this study, we developed a feeder- and xeno-free culture protocol that efficiently induced human pluripotent stem cells (iPSCs) into PLZF+/GPR125+/CD90+ spermatogonium-like cells (SLCs). These SLCs were enriched with key genes in germ cell development such as MVH, DAZL, GFRα1, NANOS3, and DMRT1. In addition, a small fraction of SLCs went through meiosis in vitro to develop into haploid cells. We further demonstrated that this chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients with non-obstructive azoospermia. Taken together, we established a powerful experimental platform to investigate human germ cell development and pathology related to male infertility.

KEYWORDS:

infertility; non-obstructive azoospermia; pluripotent stem cells; spermatogonia

PMID:
29398481
PMCID:
PMC5830957
DOI:
10.1016/j.stemcr.2018.01.001
[Indexed for MEDLINE]
Free PMC Article

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