Childs Andrew J, Saunders Philippa T K, Anderson Richard A
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Mol Hum Reprod. 2008 Sep;14(9):501-11. doi: 10.1093/molehr/gan042. Epub 2008 Aug 1.
Germ cells have a critical role in mediating the generation of genetic diversity and transmitting this information across generations. Furthermore, gametogenesis is unique as a developmental process in that it generates highly-specialized haploid gametes from diploid precursor stem cells through meiosis. Despite the importance of this process, progress in elucidating the molecular mechanisms underpinning mammalian germ cell development has been retarded by the lack of an efficient and reproducible system of in vitro culture for the expansion and trans-meiotic differentiation of germline cells. The dearth of such a culture system has rendered the study of germ cell biology refractory to the application of new high-throughput technologies such as RNA interference, leaving in vivo gene-targeting approaches as the only option to determine the function of genes believed to be involved in gametogenesis. Recent reports detailing the derivation of gametes in vitro from stem cells may provide the first steps in developing new tools to solve this problem. This review considers the developments made in modelling germ cell development using stem cells, and some of the challenges that need to be overcome to make this a useful tool for studying gametogenesis and to realize any future clinical application.
生殖细胞在介导遗传多样性的产生以及跨代传递这些信息方面发挥着关键作用。此外，配子发生作为一种发育过程具有独特性，因为它通过减数分裂从二倍体前体干细胞产生高度特化的单倍体配子。尽管这一过程很重要，但由于缺乏一种用于生殖系细胞扩增和减数分裂后分化的高效且可重复的体外培养系统，阐明哺乳动物生殖细胞发育基础分子机制的进展受到了阻碍。这种培养系统的匮乏使得生殖细胞生物学研究难以应用RNA干扰等新的高通量技术，使得体内基因靶向方法成为确定被认为参与配子发生的基因功能的唯一选择。最近详细报道了从干细胞体外衍生配子的研究，这可能是开发解决该问题新工具的第一步。本综述探讨了利用干细胞模拟生殖细胞发育所取得的进展，以及为使其成为研究配子发生的有用工具并实现未来任何临床应用而需要克服的一些挑战。
