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Oct4-induced pluripotency in adult neural stem cells

Jeong Beom Kim, Vittorio Sebastiano, Guangming Wu, Marcos J Araúzo-Bravo, Philipp Sasse, Luca Gentile, Kinarm Ko, David Ruau, Mathias Ehrich, Dirk van den Boom, Johann Meyer, Karin Hübner, Christof Bernemann, Claudia Ortmeier, Martin Zenke, Bernd K Fleischmann, Holm Zaehres, Hans R Schöler
Cell 2009 February 6, 136 (3): 411-9
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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.

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