Oct4-Induced Pluripotency in Adult Neural Stem Cells

被引:795
作者
Kim, Jeong Beom [1 ]
Sebastiano, Vittorio [1 ]
Wu, Guangming [1 ]
Arauzo-Bravo, Marcos J. [1 ]
Sasse, Philipp [2 ]
Gentile, Luca [1 ]
Ko, Kinarm [1 ]
Ruau, David [3 ]
Ehrich, Mathias [4 ]
van den Boom, Dirk [4 ]
Meyer, Johann [5 ]
Huebner, Karin [1 ]
Bernemann, Christof [1 ]
Ortmeier, Claudia [1 ]
Zenke, Martin [3 ]
Fleischmann, Bernd K. [2 ]
Zaehres, Holm [1 ]
Schoeler, Hans R. [1 ]
机构
[1] Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, NRW, Germany
[2] Univ Bonn, Inst Physiol 1, Life & Brain Ctr, D-53105 Bonn, NRW, Germany
[3] RWTH Aachen Univ Med Sch, Inst Biomed Engn, Dept Cell Biol, D-52074 Aachen, NRW, Germany
[4] SEQUENOM Inc, San Diego, CA 92121 USA
[5] Hannover Med Sch, Dept Expt Hematol, D-30625 Hannover, Germany
关键词
PRIMORDIAL GERM-CELLS; HUMAN FIBROBLASTS; SELF-RENEWAL; MOUSE; GENERATION; EXPRESSION; DERIVATION; INDUCTION; OCT4; MYC;
D O I
10.1016/j.cell.2009.01.023
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
The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem cells (1F iPS) are similar to embryonic stem cells in vitro and in vivo. Not only can these cells can be efficiently differentiated into NSCs, cardiomyocytes, and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.
引用
收藏
页码:411 / 419
页数:9
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