Renji Hospital, Sperm Development and Genetics Laboratory, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Department of Urology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
Asian J Androl. 2012 Jul;14(4):574-9. doi: 10.1038/aja.2012.3. Epub 2012 Apr 16.
Recent studies have reported that induced pluripotent stem (iPS) cells from mice and humans can differentiate into primordial germ cells. However, whether iPS cells are capable of producing male germ cells is not known. The objective of this study was to investigate the differentiation potential of mouse iPS cells into spermatogonial stem cells and late-stage male germ cells. We used an approach that combines in vitro differentiation and in vivo transplantation. Embryoid bodies (EBs) were obtained from iPS cells using leukaemia inhibitor factor (LIF)-free medium. Quantitative PCR revealed a decrease in Oct4 expression and an increase in Stra8 and Vasa mRNA in the EBs derived from iPS cells. iPS cell-derived EBs were induced by retinoic acid to differentiate into spermatogonial stem cells (SSCs), as evidenced by their expression of VASA, as well as CDH1 and GFRα1, which are markers of SSCs. Furthermore, these germ cells derived from iPS cells were transplanted into recipient testes of mice that had been pre-treated with busulfan. Notably, iPS cell-derived SSCs were able to differentiate into male germ cells ranging from spermatogonia to round spermatids, as shown by VASA and SCP3 expression. This study demonstrates that iPS cells have the potential to differentiate into late-stage male germ cells. The derivation of male germ cells from iPS cells has potential applications in the treatment of male infertility and provides a model for uncovering the molecular mechanisms underlying male germ cell development.
最近的研究报告称，来自小鼠和人类的诱导多能干细胞（iPS 细胞）可以分化为原始生殖细胞。然而，iPS 细胞是否能够产生雄性生殖细胞尚不清楚。本研究的目的是研究小鼠 iPS 细胞向精原干细胞和晚期雄性生殖细胞分化的潜能。我们采用了一种结合体外分化和体内移植的方法。使用无白血病抑制因子（LIF）的培养基从 iPS 细胞中获得类胚体（EBs）。定量 PCR 显示，iPS 细胞来源的 EBs 中 Oct4 表达减少，Stra8 和 Vasa mRNA 增加。用维甲酸诱导 iPS 细胞来源的 EBs 分化为精原干细胞（SSCs），这可以通过 VASA 以及 SSCs 的标志物 CDH1 和 GFRα1 的表达来证明。此外，这些源自 iPS 细胞的生殖细胞被移植到已用白消安预处理的受体睾丸中。值得注意的是，iPS 细胞来源的 SSCs 能够分化为从精原细胞到圆形精子细胞的雄性生殖细胞，这可以通过 VASA 和 SCP3 的表达来证明。本研究表明，iPS 细胞具有分化为晚期雄性生殖细胞的潜力。从 iPS 细胞中获得雄性生殖细胞在治疗男性不育症方面具有应用潜力，并为揭示雄性生殖细胞发育的分子机制提供了模型。
