In vitro and in vivo differentiation of induced pluripotent stem cells into male germ cells
In vitro and in vivo differentiation of induced pluripotent stem cells into male germ cells
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DOI：
10.1016/j.bbrc.2013.02.107
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发表时间：
2013-04-12
影响因子：
3.1
通讯作者：
Xu, Chen
中科院分区：
文献类型：
--
作者：
Cai, Heng;Xia, Xiaoyu;Xu, Chen
诱导多能干细胞（iPSC）系的引入是干细胞研究领域的重大突破。然而，这些细胞系之间的多能性程度往往是可变的，因为它们的不同的表观遗传特征。通过逆转录病毒转染人类转录因子Oct4、Sox2、Klf4和c-Myc，建立了小鼠iPS细胞系4.1；这个系的种系能力尚未确定。本研究在体内和体外诱导miPS-4.1细胞向男性生殖细胞分化。在体外模型中，miPS-4.1细胞的行为与分化的小鼠胚胎干细胞（ESCs）相同。我们获得了碱性磷酸酶（AP）活性阳性的原始生殖细胞样细胞（PGC-LC）。在连续培养中，这些细胞表达多能性标记物Oct4和雄性种系标记物C-kit和MVH。在我们的体内模型中，miPS-4.1细胞与新生儿睾丸细胞悬液共移植。我们观察到异位重建的精管结构，miPS-4.1细胞在其中归巢和发育。总之，我们成功地诱导了miPS-4.1细胞向男性生殖细胞的分化，尽管它们具有表观遗传特征。我们的研究为研究男性生殖细胞发育机制提供了一个系统，并可能有助于在未来提供有效的治疗男性不育的方法。(C) 2013爱思唯尔公司版权所有。
The introduction of induced pluripotent stem cell (iPSC) lines has been a breakthrough in the field of stem cell research. However, the extent of pluripotency among those cell lines tends to be variable due to their different epigenetic signatures. Mouse iPS cell line 4.1 has been established via retroviral transfer of human transcription factors Oct4, Sox2, Klf4, and c-Myc; the germline competence of this line has not been determined. In the present study, we induced the differentiation of miPS-4.1 cells into male germ cells, in vivo and in vitro. In the in vitro model, the behavior of miPS-4.1 cells was identical to that of differentiating mouse embryonic stem cells (ESCs). We obtained primordial germ cell-like cells (PGC-LC) that were positive for alkaline phosphatase (AP) activity. In continuous culture, these cells expressed pluripotent marker Oct4 and male germline markers C-kit and MVH. For our in vivo model, miPS-4.1 cells were co-transplanted with neonatal testicular cell suspension. We observed ectopically reconstituted seminiferous tubule structures, in which the miPS-4.1 cells were homing and developing. In conclusion, we successfully induced the differentiation of miPS-4.1 cells into male germ cells, albeit their epigenetic characteristics. Our study provides a system to examine the mechanisms of male germ cell development and might help to supply an effective treatment for male infertility in the future. (C) 2013 Elsevier Inc. All rights reserved.