Nature 454, 646-650 (31 July 2008) | doi:10.1038/nature07061; Received 20 March 2008; Accepted 8 May 2008; Published online 29 June 2008

Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors

Jeong Beom Kim1,3, Holm Zaehres1,3, Guangming Wu1, Luca Gentile1, Kinarm Ko1, Vittorio Sebastiano1, Marcos J. Araúzo-Bravo1, David Ruau2, Dong Wook Han1, Martin Zenke2 & Hans R. Schöler1

  1. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, NRW, Germany
  2. Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Pauwelsstrasse 30, 52074 Aachen, NRW, Germany
  3. These authors contributed equally to this work.

Correspondence to: Hans R. Schöler1 Correspondence and requests for materials should be addressed to H.R.S. (Email: schoeler@mpi-muenster.mpg.de).

Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc and Klf4 (refs 1–11). Considering that ectopic expression of c-Myc causes tumorigenicity in offspring2 and that retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells. These two-factor iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimaeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.


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