Abstract
Oct-3/4 (Oct-3/Oct-4/POU5F1) is a critical regulator of embryonic stem (ES) cell differentiation, though its role in tissue stem cells that persist in differentiated tissues has not been shown. Here, we show that Oct-3/4 is expressed in neurospheres (NS) composed of neural stem cells and neural progenitor cells and that up- or down-regulation of Oct-3/4 by using adenovirus vectors influences cell fate. Oct-3/4 down-regulation accelerates neuronal differentiation of progenitor cells while its sustained expression prevents neuronal differentiation. Transplantation of neurospheres into the adult rat brain shows that down-regulation of Oct-3/4 promotes differentiation of NS cells in vivo. Our findings indicate that Oct-3/4 is an essential regulator of NS cell differentiation and suggest that the modulation of Oct-3/4 could be a useful tool in clinical application of NS cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Age Factors
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Animals
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Biomarkers / metabolism
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Brain / cytology
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Brain / embryology
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Brain / metabolism*
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Cell Differentiation / genetics*
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Cell Proliferation
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Down-Regulation / genetics
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Genetic Vectors
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Graft Survival / genetics
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Intermediate Filament Proteins / metabolism
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Mice
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Mice, Inbred ICR
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Nerve Tissue Proteins / metabolism
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Nestin
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Neuroglia / cytology
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Neuroglia / metabolism
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Neurons / cytology
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Neurons / metabolism*
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Octamer Transcription Factor-3
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Spheroids, Cellular
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Stem Cell Transplantation
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Stem Cells / cytology
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Stem Cells / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Up-Regulation / genetics
Substances
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Biomarkers
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DNA-Binding Proteins
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Intermediate Filament Proteins
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Nerve Tissue Proteins
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Nes protein, mouse
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Nes protein, rat
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Nestin
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Octamer Transcription Factor-3
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Pou5f1 protein, mouse
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Transcription Factors