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

نویسندگان

  • Yuncheng Zhao
  • Shicheng Ye
  • Dongli Liang
  • Pengxiang Wang
  • Jing Fu
  • Qing Ma
  • Ruijiao Kong
  • Linghong Shi
  • Xueping Gong
  • Wei Chen
  • Wubin Ding
  • Wenjing Yang
  • Zijue Zhu
  • Huixing Chen
  • Xiaoxi Sun
  • Jun Zhu
  • Zheng Li
  • Yuan Wang
چکیده

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.

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عنوان ژورنال:

دوره 10  شماره 

صفحات  -

تاریخ انتشار 2018