Reference : Direct reprogramming of fibroblasts into neural stem cells by defined factors.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Direct reprogramming of fibroblasts into neural stem cells by defined factors.
Han, Dong Wook [> >]
Tapia, Natalia [> >]
Hermann, Andreas [> >]
Hemmer, Kathrin [> >]
Hoing, Susanne [> >]
Arauzo-Bravo, Marcos J. [> >]
Zaehres, Holm [> >]
Wu, Guangming [> >]
Frank, Stefan [> >]
Moritz, Soren [> >]
Greber, Boris [> >]
Yang, Ji Hun [> >]
Lee, Hoon Taek [> >]
Schwamborn, Jens Christian mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Storch, Alexander [> >]
Scholer, Hans R. [> >]
Cell Stem Cell
Yes (verified by ORBilu)
United States
[en] Animals ; Antigens, Differentiation/biosynthesis/genetics ; Cell Dedifferentiation ; Fibroblasts/cytology/metabolism ; Gene Expression Regulation/genetics ; Induced Pluripotent Stem Cells/cytology/metabolism ; Mice ; Neural Stem Cells/cytology/metabolism ; Transcription Factors/biosynthesis/genetics
[en] Recent studies have shown that defined sets of transcription factors can directly reprogram differentiated somatic cells to a different differentiated cell type without passing through a pluripotent state, but the restricted proliferative and lineage potential of the resulting cells limits the scope of their potential applications. Here we show that a combination of transcription factors (Brn4/Pou3f4, Sox2, Klf4, c-Myc, plus E47/Tcf3) induces mouse fibroblasts to directly acquire a neural stem cell identity-which we term as induced neural stem cells (iNSCs). Direct reprogramming of fibroblasts into iNSCs is a gradual process in which the donor transcriptional program is silenced over time. iNSCs exhibit cell morphology, gene expression, epigenetic features, differentiation potential, and self-renewing capacity, as well as in vitro and in vivo functionality similar to those of wild-type NSCs. We conclude that differentiated cells can be reprogrammed directly into specific somatic stem cell types by defined sets of specific transcription factors.
Copyright (c) 2012 Elsevier Inc. All rights reserved.

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