Oct-3/4 repression accelerates differentiation of neural progenitor cells in vitro and in vivo.
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.
Okuda
Tomohiro
T
Department of Molecular Therapeutics, Tokyo Metropolitan Institute for Neuroscience, Japan.
Tagawa
Kazuhiko
K
Qi
Mei-Ling
ML
Hoshio
Masataka
M
Ueda
Hiroko
H
Kawano
Hitoshi
H
Kanazawa
Ichiro
I
Muramatsu
Masami
M
Okazawa
Hitoshi
H
D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005822:Genetic Vectors; D006085:Graft Survival / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D050814:Octamer Transcription Factor-3; D018874:Spheroids, Cellular; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; D004268:DNA-Binding Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors