Oct-3/4 repression accelerates differentiation of neural progenitor cells in vitro and in vivo

Oct-3/4 (O1ct-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- ordown-regulation of Oct-3/4 by using adenovirus, vectors influences cell fate. Oct-3/4 downregulation 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. (C) 2004 Elsevier B.V. All rights reserved.