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Oct4-Induced Pluripotency in Adult Neural Stem Cells
Jeong Beom Kim1,Vittorio Sebastiano1,Guangming Wu1,Marcos J. Araúzo-Bravo1,Philipp Sasse2,Luca Gentile1,Kinarm Ko1,David Ruau3,Mathias Ehrich4,Dirk van den Boom4,Johann Meyer5,Karin Hübner1,Christof Bernemann1,Claudia Ortmeier1,Martin Zenke3,Bernd K. Fleischmann2,Holm Zaehres1andHans R. Sch?ler1,,
1 Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, R?ntgenstrasse 20, 48149 Münster, NRW, Germany
2 Institute of Physiology I, Life & Brain Center, University of Bonn, 53105 Bonn, NRW, Germany
3 Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Pauwelsstrasse 30, 52074 Aachen, NRW, Germany
4 SEQUENOM Inc., 3595 John Hopkins Court, San Diego, CA 92121, USA
5 Hannover Medical School, Department of Experimental Hematology, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
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 invitro and invivo. Not only can these cells can be efficiently differentiated into NSCs, cardiomyocytes, and germ cells invitro, but they are also capable of teratoma formation and germline transmission invivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.
