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30 - Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors

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Speaker : Dong Wook Han, Ph.D. (건국대학교/Max Planck Institute for Molecular Biomedicine)

Date : 2012-03-27

Location : Room 106Pharmacy Hall, Dankook University

Abstract : Recent studies have shown that defined sets of transcription factors can directly reprogram differentiated somatic cells to a different differntiatied 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 application. 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.

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