A Germ Cell-specific Gene, Prmt5, Works in Somatic Cell Reprogramming

被引:56
作者
Nagamatsu, Go [1 ,4 ]
Kosaka, Takeo [2 ]
Kawasumi, Miyuri [3 ]
Kinoshita, Taisuke
Takubo, Keiyo
Akiyama, Hideo [5 ]
Sudo, Tetsuo [5 ]
Kobayashi, Takashi [3 ]
Oya, Mototsugu [2 ]
Suda, Toshio
机构
[1] Keio Univ, Sch Med, Dept Cell Differentiat, Sakaguchi Lab,Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Urol, Tokyo 1608582, Japan
[3] Keio Univ, Sch Med, Ctr Integrated Med Res, Tokyo 1608582, Japan
[4] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan
[5] Toray New Frontiers Res Labs, Kanagawa 2488555, Japan
基金
日本科学技术振兴机构;
关键词
PLURIPOTENT STEM-CELLS; ARGININE METHYLATION; MOUSE; GENERATION; INDUCTION; HISTONE; EXPRESSION; DYNAMICS; LINEAGE; PRDM14;
D O I
10.1074/jbc.M110.216390
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:10641 / 10648
页数:8
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