Article (Scientific journals)
Direct reprogramming of fibroblasts into neural stem cells by defined factors.
Han, Dong Wook; Tapia, Natalia; Hermann, Andreas et al.
2012In Cell Stem Cell, 10 (4), p. 465-72
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Keywords :
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
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
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 ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Storch, Alexander
Scholer, Hans R.
More authors (6 more) Less
Language :
English
Title :
Direct reprogramming of fibroblasts into neural stem cells by defined factors.
Publication date :
2012
Journal title :
Cell Stem Cell
ISSN :
1875-9777
Publisher :
Cell Press, United States - Massachusetts
Volume :
10
Issue :
4
Pages :
465-72
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2012 Elsevier Inc. All rights reserved.
Available on ORBilu :
since 21 June 2013

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