A germ cell-specific gene, Prmt5, works in somatic cell reprogramming.
A germ cell-specific gene, Prmt5, works in somatic cell reprogramming.
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DOI：
10.1074/jbc.m110.216390
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发表时间：
2011-03-25
期刊：
影响因子：
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通讯作者：
Suda T
中科院分区：
文献类型：
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作者：
Nagamatsu G;Kosaka T;Kawasumi M;Kinoshita T;Takubo K;Akiyama H;Sudo T;Kobayashi T;Oya M;Suda T
生殖细胞具有在体内发育期间获得全能性以及在体外适当条件下产生多能干细胞的独特能力。最近的研究表明，体细胞被实验性地转化为多能干细胞，这表明在原始生殖细胞（PGCs）中表达的基因，如Oct 3/4，Sox 2和Lin 28，参与了这种重编程。这些研究结果表明，PGCs可能是有用的识别因子，成功和有效地重编程体细胞成全能和/或多能干细胞。在这里，我们发现Blimp-1，Prdm 14和Prmt 5，每一个都对PGC的发育至关重要，有可能将体细胞重编程为多能干细胞。其中，Prmt 5对导入Prmt 5、Klf 4和Oct 3/4的小鼠胚胎成纤维细胞表现出显著的重编程。由此产生的细胞表现出多能基因表达，畸胎瘤的形成，和生殖系传递嵌合小鼠，所有这些都是与胚胎干细胞诱导的区别。这些数据表明，在生殖细胞发育中起重要作用的一些因子在体细胞重编程中也很活跃。
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.