Author: ["Dong Wook Han","Boris Greber","Guangming Wu","Natalia Tapia","Marcos J. Araúzo-Bravo","Kinarm Ko","Christof Bernemann","Martin Stehling","Hans R. Schöler"]
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Abstract
The four transcription factors Oct4, Sox2, Klf4 and c-myc induce somatic cells to reprogramme to an early embryonic stem cell state. When expressed in somatic cells under culture conditions that are normally used for stem cells derived from mouse epiblast tissue of post-implantation embryos (EpiSCs), these factors drive reprogramming to a state that closely resembles EpiSCs, highlighting the importance of culture environment in determining the outcome of reprogramming. Epiblast stem cells (EpiSCs) derived from epiblast tissue of post-implantation embryos are pluripotent and can give rise to all three germ layers in teratoma assays1,2. Introduction of the four transcription factors Oct4, Sox2, Klf4 and c-Myc into somatic cells has been shown to generate induced pluripotent stem cells (iPSCs) that are very similar to embryonic stem cells (ESCs) in a number of characteristics3,4,5,6. However, generation of EpiSCs by the direct reprogramming of somatic cells using these transcription factors has not been shown to date. Here, we show that these transcription factors can be used to directly generate induced EpiSCs (iEpiSCs) under EpiSC culture conditions. iEpiSCs resemble EpiSCs in morphology, gene expression pattern, epigenetic status and chimaera-forming capability. This study demonstrates that the culture environment in transcription factor-mediated reprogramming determines the cell fate of the reprogrammed cell. We therefore hypothesize that it will eventually be possible to shape the identity of a directly reprogrammed cell simply by modulating culture conditions.Cite this article
Han, D., Greber, B., Wu, G. et al. Direct reprogramming of fibroblasts into epiblast stem cells. Nat Cell Biol 13, 66–71 (2011). https://doi.org/10.1038/ncb2136 