诱导多能干细胞体外定向分化为雄性生殖细胞研究进展

doi:10.3864/j.issn.0578-1752.2014.16.016

摘要/Abstract

摘要： 诱导多能干细胞（induced pluripotent stem cells, iPS）是借助基因导入技术将某些转录因子导入人或动物的体细胞，使体细胞重编程而得到的多能性细胞。iPS细胞来源丰富，研究表明利用不同的载体诱导系统或不同的转录因子组合，多种体细胞都可被重编程为iPS细胞，如成纤维细胞、肝细胞、角质细胞及脐带血细胞等。作为干细胞中新的一员，iPS细胞在克隆形态、基因表达模式、表面标志物、拟胚体形成、畸胎瘤及嵌合体形成（小鼠）、分化能力等方面与胚胎干细胞（embryonic stem cell, ESC）非常相似。与胚胎干细胞一样，在特定的诱导条件下，iPS细胞在体外可被诱导分化为多种细胞，如心肌细胞、血细胞、生殖细胞等，进一步拉近了干细胞和临床疾病治疗的距离，iPS细胞也成为细胞治疗及组织器官再生最有前景的种子细胞，在细胞替代性治疗、发病机理研究及新药筛选方面具有潜在价值。雄性不育不仅影响人类正常健康生活，对畜牧业的发展也极为不利。国内外的研究成果表明，给予适当的诱导物及诱导条件，人和小鼠的iPS细胞体外可被诱导分化为原始生殖细胞（primordial germ cells, PGCs）、精子细胞及其前体细胞。这些研究不仅避免了胚胎干细胞研究领域存在的取材困难、免疫排斥和伦理道德等问题，还为揭示雄性生殖细胞的发育机制及研究雄性不育提供了较好的研究平台。由人iPS细胞诱导得到的雄性配子可为患者提供自身的雄性配子产生后代，避免了免疫排斥问题，为未来治疗雄性不育带来曙光。iPS细胞体外诱导分化技术对现代畜牧业发展也具有巨大的潜在应用价值，可进行转基因动物的生产。现从不同的诱导剂、不同的培养条件及iPS细胞体外诱导分化优势等方面，对iPS细胞体外定向诱导分化为雄性生殖细胞的研究进展及应用前景进行综述和展望。

关键词: 诱导多能干细胞, 诱导分化, 精原干细胞, 雄性生殖细胞

Abstract: Induced pluripotent stem cells (iPS cells) refers to reprograming animals or human somatic cells by gene transfer technology, i.e. using so-called packed viral vectors or particles to infect the cells to be induced. Different somatic cells can be induced into iPS cells through different vectors or different transcription factors combination, such as fibroblasts, hepatocytes, keratinocytes and cord blood, etc. As a new member, iPS cells were similar to embryonic stem cells, i.e. clonal morphology, gene expression pattern, surface marker, embryoid bodies formation, differentiative capacity, teratoma and chimeras (in mice) and so on. Just like ESCs, studies have shown that iPS cells can be induced into different cells in vitro under the conditions of specific induction, including myocardial cells, blood cells and germ cells. It shortens the distance between stem cells and clinical disease, Therefore iPS cells have become the most promising seed cells in cell therapy and tissue organ regeneration, and they have a potential value in the cells’ alternative treatment, pathogenesis research and new drug screening simultaneously. Male sterility not only affects human normal life, but is also very adverse to the development of animal husbandry. Great progress has been made in that iPS cells from humans and mice can be differentiated into primordial germ cells (PGCs), spermatozoa and their precursors. These findings can help not only avoid the difficulties in obtaining ESCs, immune rejection and ethical problems, which may be aroused by using embryonic stem cells, but also provide a good research platform for revealing the developmental mechanism of male germ cells. Patients can use their iPS cells derived male gametes to reproduction. Therefore, differentiation of iPS cells into male germ cells brings new hope for the treatment of male sterility in the future. In addition, differentiation of iPS cells in vitro has broad application potentials for modern animal husbandry. It can be used to produce the transgenic animals. Here, the authors highlighted the advances in research of the differentiation of iPS cells into male germ cells in vitro and its potential application prospects from the different culture conditions and inducers and the prospects in application of the differentiation of iPS cells.

Key words: induced pluripotent stem cells, differentiation, spermatogonial stem cells, male germ cells

中图分类号:

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杜军慧, 曹文广. 诱导多能干细胞体外定向分化为雄性生殖细胞研究进展[J]. 中国农业科学, 2014, 47(16): 3308-3314.

DU Jun-Hui, CAO Wen-Guang. Advances in Differentiation of iPS Cells into Male Germ Cells[J]. Scientia Agricultura Sinica, 2014, 47(16): 3308-3314.

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