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

　　馮立新研究組誘導(dǎo)精原干細(xì)胞來源的卵細(xì)胞大小如體內(nèi)正常卵細(xì)胞并表達(dá)卵細(xì)胞特異標(biāo)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(dá)發(fā)生變化，維持精原干細(xì)胞相關(guān)的基因被關(guān)閉，而卵細(xì)胞特異表達(dá)的基因在X染色體上被激活。同時，干細(xì)胞來源的卵細(xì)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(xì)胞具有被誘導(dǎo)成卵細(xì)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(diào)控生殖細(xì)胞命運以及表觀遺傳印跡的建立提供理想的模型。相關(guān)研究成果已于近日發(fā)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 plu**otent 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 plu**otency 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.