Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582, Japan.
J Biol Chem. 2011 Mar 25;286(12):10641-8. doi: 10.1074/jbc.M110.216390. Epub 2011 Jan 26.
Germ cells possess the unique ability to acquire totipotency during development in vivo as well as give rise to pluripotent stem cells under the appropriate conditions in vitro. Recent studies in which somatic cells were experimentally converted into pluripotent stem cells revealed that genes expressed in primordial germ cells (PGCs), such as Oct3/4, Sox2, and Lin28, are involved in this reprogramming. These findings suggest that PGCs may be useful for identifying factors that successfully and efficiently reprogram somatic cells into toti- and/or pluripotent stem cells. Here, we show that Blimp-1, Prdm14, and Prmt5, each of which is crucial for PGC development, have the potential to reprogram somatic cells into pluripotent stem cells. Among them, Prmt5 exhibited remarkable reprogramming of mouse embryonic fibroblasts into which Prmt5, Klf4, and Oct3/4 were introduced. The resulting cells exhibited pluripotent gene expression, teratoma formation, and germline transmission in chimeric mice, all of which were indistinguishable from those induced with embryonic stem cells. These data indicate that some of the factors that play essential roles in germ cell development are also active in somatic cell reprogramming.
生殖细胞具有在体内发育过程中获得全能性的独特能力，以及在适当的条件下在体外产生多能干细胞的能力。最近的研究表明，实验中将体细胞转化为多能干细胞时，表达于原始生殖细胞（PGC）中的基因，如 Oct3/4、Sox2 和 Lin28 等，参与了这种重编程。这些发现表明 PGC 可能有助于鉴定成功且高效地将体细胞重编程为全能性和/或多能干细胞的因子。在这里，我们表明 Blimp-1、Prdm14 和 Prmt5 中的每一个对于 PGC 发育都是至关重要的，都具有将体细胞重编程为多能干细胞的潜力。其中，Prdm14 表现出对小鼠胚胎成纤维细胞的显著重编程，将 Prmt5、Klf4 和 Oct3/4 引入其中。所得细胞表现出多能基因表达、畸胎瘤形成和嵌合小鼠中的种系传递，所有这些都与胚胎干细胞诱导的细胞无法区分。这些数据表明，在生殖细胞发育中起重要作用的一些因子也在体细胞重编程中起作用。
