近日，上海交通大学冯立新研究小组报道一个全新的体外诱导精子和卵子的方法。冯立新研究员采用的方法可从雄性胚胎干细胞（XY 染色体）在体外同时生成游动的精子和卵子。更为重要的是他们的研究进一步阐明了从胚胎干细胞生成精子和卵子分子机理，是这一领域研究的重大突破。

之前，科学家们已经证明了胚胎干细胞（ESC）能在体外分化出胚性生殖细胞，冯立新研究小组体外诱导分化并不经过类胚体形成，通过利用转基因技术直接从胚胎干细胞转化为生殖细胞。Dazl基因是表达生殖细胞特异RNA结合蛋白的基因，人和多种动物的Dazl基因是精子发生的重要调控因子，Dazl基因突变或表达缺乏将导致精子发生过程减数分裂障碍和雄性不育。研究者通过Dazl基因的异位表达，最终在体外将小鼠胚胎干细胞同时诱导出了游动的精子和卵子。此外， Dazl基因的瞬时过量表达使Nanog受到抑制，但是小鼠胚胎干细胞核抗原被诱导成生殖细胞。Dazl基因敲低导致了生殖细胞部分标记物基因表达降低，比如说Stella，MVH和Prdm1等。冯立新研究小组不仅证明了Dazl基因是控制生殖细胞分化的一个主要控制基因，而且通过Dazl基因异位表达诱导出小鼠胚胎干细胞在体外分化成了生殖细胞精子和卵子。

2009年10月28日，斯坦福大学人类胚胎干细胞及再生组织医学研究小组Kehkooi Kee 等在Nature发表了他们最新的研究成果，研究者在实验室通过人体干细胞制造出人工精子和卵子，这一研究成果进一步证实了冯立新研究团队所做的工作的前沿性和重要性，同时也表明我国在体外诱导干细胞生成精子和卵子研究处于国际领先地位。

Journal of Molecular Cell Biology (2009), 1–11 doi:10.1093/jmcb/mjp026

Dazl Promotes Germ Cell Differentiation from Embryonic Stem Cells

Zhuo Yu1, Ping Ji1, Jinping Cao1, Shu Zhu1, Yao Li2, Lin Zheng3, Xuejin Chen2, and Lixin Feng1,*

1 Laboratory for Germ Cell Research, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
2 Department of Laboratory Animal Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3 Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

It has been demonstrated that through the formation of embryoid bodies (EBs) germ cells can be derived from embryonic stem (ES) cells. Here, we describe a transgene expression approach to derive germ cells directly from ES cells in vitro without EB formation. Through the ectopic expression of Deleted in Azoospermia-Like (Dazl), a germ cell-specific RNA-binding protein,both motile tailed-sperm and oocytes were induced from mouse ES (mES) cells in culture. Furthermore, transient overexpression of Dazl led to suppression of Nanog but induced germ cell nuclear antigen in mES cells. Dazl knockdown resulted in reduction in the expression of germ cell markers including Stella, MVH and Prdm1. Our study indicates that Dazl is a master gene controlling germ cell differentiation and that ectopic expression of Dazl promotes the dynamic differentiation of mouse ES cells into gametes in vitro.