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.
[1]East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China.
[2]East China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China.
[3]Michigan State Univ, Dept Anim Sci, E Lansing, MI 48824 USA.
[4]Fudan Univ, Obstet & Gynecol Hosp, Shanghai 200011, Peoples R China.
[5]NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[6]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Shanghai Key Lab Reprod Med, Dept Androl,Urol Med Ctr, Shanghai 200080, Peoples R China.
(8.0+极速模式)