Direct reprogramming of human neural stem cells by OCT4

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Abstract

Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4)1,2,3,4,5,6,7. We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells8. Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.

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Figure 1: 1F human NSC-derived iPS cell colony formation and cell line characterization.
Figure 2: Expression levels of pluripotent markers and DNA methylation analysis in human NSC-derived iPS cells.
Figure 3: In vitro differentiation of human NSC-derived iPS cells into all three germ layers.
Figure 4: In vivo pluripotency and global gene expression profile of human NSC-derived iPS cells.

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Primary accessions

Gene Expression Omnibus

Data deposits

The microarray data sets are available from GEO (Gene Expression Omnibus) under accession number GSE15355. Human NiPS cells are in the process of being deposited in the UK Stem Cell Bank.

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Acknowledgements

We thank B. Schäfer for histology, T. Kitamura for the pMX retroviral vector and A. Malapetsas and S. Kölsch for editing. This work has been supported, in part, by a grant from the German Federal Ministry of Education and Research BMBF 01GN0811 and in part by a grant by the Deutsche Forschungsgemeinschaft DFG SCHO 340/4-1.

Author Contributions J.B.K., project design, generation and characterization of iPS cells, preparation of manuscript; B.G., M.J.A.-B., J.M., characterization of iPS cells; K.I.P., providing human NSCs; H.Z., project design, generation of iPS cells, preparation of manuscript; H.R.S., project design, preparation of manuscript.

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Correspondence to Hans R. Schöler.

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This file contains Supplementary Methods, Supplementary Tables 1-2 and Supplementary Figures 1-8 with Legends. (PDF 4717 kb)

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Kim, J., Greber, B., Araúzo-Bravo, M. et al. Direct reprogramming of human neural stem cells by OCT4. Nature 461, 649–653 (2009) doi:10.1038/nature08436

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