Institute of Medical Sciences, Shanghai JiaoTong University School of Medicine, 280 Chongqing S, Road, Shanghai, 200025, China.
Cell Biosci. 2012 Aug 6;2(1):27. doi: 10.1186/2045-3701-2-27.
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.
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 gave 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.
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.
在正常发育过程中，原始生殖细胞（PGC）来源于上胚层，是精原细胞和卵原细胞的前体细胞。在培养条件下，PGC 可以在各种生长因子的存在下诱导去分化为多能胚胎生殖（EG）细胞。最近的几项研究表明，在某些培养条件下，精原干细胞（SSC）也可以作为胚胎干细胞（ES）样细胞回复到多能性。然而，SSC 向 PGC 的潜在去分化或 SSC 产生卵母细胞的潜在能力以前尚未得到证明。
我们报告说，在培养条件下，雄性小鼠 SSC 可以转化为卵母细胞样细胞。这些 SSC 衍生的卵母细胞（SSC-Oocs）大小与正常小鼠成熟卵母细胞相似。它们表达卵母细胞特异性标记物，并通过孤雌生殖产生胚胎。有趣的是，这些 SSC-Oocs 中的 Y 和 X 连锁睾丸特异性基因显著下调或关闭，而卵母细胞特异性 X 连锁基因被激活。基因表达谱似乎在整个 X 染色体上切换到卵母细胞。此外，这些卵母细胞样细胞失去了父系印迹，但获得了母系印迹。
我们的数据表明，SSC 可能具有被重新编程为卵母细胞的潜力，同时伴随着相应的表观遗传逆转。这项研究不仅为 SSC 的显著可塑性提供了进一步的证据，还为解析配子发生过程中生殖细胞命运决定和印迹建立的分子和表观遗传调控提供了一个潜在的系统。
