精原干細胞能轉化成卵細胞已經成為可能

　　上海交通大學醫學院馮立新研究組新近研究發現精原干細胞可以被誘導形成卵細胞。在正常發育過程中，由上胚層細胞來源的原始生殖祖細胞(primordialgermcells,PGCs)是精原干細胞和卵母細胞的共同前體細胞。以往的研究發現在一定的培養條件下，精原干細胞可被誘導成具有多能性的干細胞。而另一研究顯示具有多能性的胚胎干細胞可分化發育成PGCs和卵細胞。而精原干細胞轉分化為卵細胞的研究還未見報道。

　　馮立新研究組誘導精原干細胞來源的卵細胞大小如體內正常卵細胞并表達卵細胞特異標志物，體外可受精和形成孤雌胚胎。其Y和X染色體上的基因表達發生變化，維持精原干細胞相關的基因被關閉，而卵細胞特異表達的基因在X染色體上被激活。同時，干細胞來源的卵細胞丟失父方表觀遺傳印跡，獲得母方表觀遺傳印跡。此研究證明精原干細胞具有被誘導成卵細胞的潛能，顯示其極強的可塑性。該研究可為分析分子和表觀遺傳調控生殖細胞命運以及表觀遺傳印跡的建立提供理想的模型。相關研究成果已于近日發表在Cell&Bioscience雜志。

　　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.