Journal
STEM CELL REPORTS
Volume 10, Issue 2, Pages 509-523Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.01.001
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Funding
- Ministry of Science and Technology of China [2016YFA0100300, 2014CB964800]
- National Natural Science Foundation of China [31471347, 31771655]
- Science and Technology Commission of Shanghai Municipality [16JC1404200]
- National High Technology Research and Development Program, China [2015AA020404, SHDC1205123]
- National Heart Lung Blood Institute, USA [1ZICHL006058]
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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, GFR alpha 1, 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.
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