精原干细胞能转化成卵细胞已经成为可能

　　上海交通大学医学院冯立新研究组新近研究发现精原干细胞可以被诱导形成卵细胞。在正常发育过程中，由上胚层细胞来源的原始生殖祖细胞(primordialgermcells,PGCs)是精原干细胞和卵母细胞的共同前体细胞。以往的研究发现在一定的培养条件下，精原干细胞可被诱导成具有多能性的干细胞。而另一研究显示具有多能性的胚胎干细胞可分化发育成PGCs和卵细胞。而精原干细胞转分化为卵细胞的研究还未见报道。

　　冯立新研究组诱导精原干细胞来源的卵细胞大小如体内正常卵细胞并表达卵细胞特异标志物，体外可受精和形成孤雌胚胎。其Y和X染色体上的基因表达发生变化，维持精原干细胞相关的基因被关闭，而卵细胞特异表达的基因在X染色体上被激活。同时，干细胞来源的卵细胞丢失父方表观遗传印迹，获得母方表观遗传印迹。此研究证明精原干细胞具有被诱导成卵细胞的潜能，显示其极强的可塑性。该研究可为分析分子和表观遗传调控生殖细胞命运以及表观遗传印迹的建立提供理想的模型。相关研究成果已于近日发表在Cell&Bioscience杂志。

　　Oocyte-like Cells Induced from Mouse Spermatogonial Stem Cells

　　Lu Wang, Jinping Cao, Ping Ji, Di Zhang, Lianghong Ma, Martin Dym, Zhuo Yu and Lixin Feng

　　Background

　　During normal development primordial germ cells (PGCs) derived from the epiblast are the precursors of spermatogonia and oogonia. In culture, PGCs can be induced to dedifferentiate to pluripotent embryonic germ (EG) cells in the presence of various growth factors. Several recent studies have now demonstrated that spermatogonial stem cells (SSCs) can also revert back to pluripotency as embryonic stem (ES)-like cells under certain culture conditions. However, the potential dedifferentiation of SSCs into PGCs or the potential generation of oocytes from SSCs has not been demonstrated before.

　　Results

　　We report that mouse male SSCs can be converted into oocyte-like cells in culture. These SSCs-derived oocytes (SSC-Oocs) were similar in size to normal mouse mature oocytes. They expressed oocyte-specific markers and give rise to embryos through parthenogenesis. Interestingly, the Y- and X-linked testis-specific genes in these SSC-Oocs were significantly down-regulated or turned off, while oocyte-specific X-linked genes were activated. The gene expression profile appeared to switch to that of the oocyte across the X chromosome. Furthermore, these oocyte-like cells lost paternal imprinting but acquired maternal imprinting.

　　Conclusions

　　Our data demonstrate that SSCs might maintain the potential to be reprogrammed into oocytes with corresponding epigenetic reversals. This study provides not only further evidence for the remarkable plasticity of SSCs but also a potential system for dissecting molecular and epigenetic regulations in germ cell fate determination and imprinting establishment during gametogenesis.