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          Institute: MPI für molekulare Biomedizin     Collection: Yearbook 2013     Display Documents



  history
ID: 648336.0, MPI für molekulare Biomedizin / Yearbook 2013
Direct reprogramming of fibroblasts into neural stem cells by defined factors
Authors:Han, D. W.; Tapia, N.; Hermann, A.; Hemmer, K.; Höing, S.; Arauzo-Bravo, M. J.; Zaehres, H.; Wu, G.; Frank, S.; Moritz, S.; Greber, B.; Yang, J. H.; Lee, H. T.; Schwamborn, J. C.; Storch, A.; Schöler, H. R.
Date of Publication (YYYY-MM-DD):2012-04-06
Title of Journal:Cell Stem Cell
Volume:10
Issue / Number:4
Start Page:465
End Page:472
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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.
Free 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
External Publication Status:published
Document Type:Article
Communicated by:keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:%G eng
Identifiers:ISSN:1875-9777 (Electronic) %R 10.1016/j.stem.2012.02.0... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/22445517 [ID No:2]
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