Zhou Quan, Wang Mei, Yuan Yan, Wang Xuepeng, Fu Rui, Wan Haifeng, Xie Mingming, Liu Mingxi, Guo Xuejiang, Zheng Ying, Feng Guihai, Shi Qinghua, Zhao Xiao-Yang, Sha Jiahao, Zhou Qi
State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; College of the Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Cell Stem Cell. 2016 Mar 3;18(3):330-40. doi: 10.1016/j.stem.2016.01.017. Epub 2016 Feb 25.
In vitro generation of functional gametes is a promising approach for treating infertility, although faithful replication of meiosis has proven to be a substantial obstacle to deriving haploid gamete cells in culture. Here we report complete in vitro meiosis from embryonic stem cell (ESC)-derived primordial germ cells (PGCLCs). Co-culture of PGCLCs with neonatal testicular somatic cells and sequential exposure to morphogens and sex hormones reproduced key hallmarks of meiosis, including erasure of genetic imprinting, chromosomal synapsis and recombination, and correct nuclear DNA and chromosomal content in the resulting haploid cells. Intracytoplasmic injection of the resulting spermatid-like cells into oocytes produced viable and fertile offspring, showing that this robust stepwise approach can functionally recapitulate male gametogenesis in vitro. These findings provide a platform for investigating meiotic mechanisms and the potential generation of human haploid spermatids in vitro.
体外生成功能性配子是治疗不孕症的一种有前景的方法，尽管事实证明，减数分裂的忠实复制是在培养中获得单倍体配子细胞的一个重大障碍。在此，我们报告了从胚胎干细胞（ESC）衍生的原始生殖细胞（PGCLC）中实现完全的体外减数分裂。将PGCLC与新生睾丸体细胞共培养，并依次暴露于形态发生素和性激素下，再现了减数分裂的关键特征，包括遗传印记的消除、染色体联会和重组，以及所得单倍体细胞中正确的核DNA和染色体含量。将所得的类精子细胞进行胞浆内注射到卵母细胞中产生了存活且可育的后代，表明这种稳健的逐步方法能够在体外功能性地重现雄性配子发生。这些发现为研究减数分裂机制以及体外潜在生成人类单倍体精子细胞提供了一个平台。
