Okuda Tomohiro, Tagawa Kazuhiko, Qi Mei-Ling, Hoshio Masataka, Ueda Hiroko, Kawano Hitoshi, Kanazawa Ichiro, Muramatsu Masami, Okazawa Hitoshi
Department of Molecular Therapeutics, Tokyo Metropolitan Institute for Neuroscience, Japan.
Brain Res Mol Brain Res. 2004 Dec 6;132(1):18-30. doi: 10.1016/j.molbrainres.2004.08.021.
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.
八聚体转录因子3/4（Oct-3/Oct-4/POU5F1）是胚胎干细胞（ES细胞）分化的关键调节因子，不过其在分化组织中持续存在的组织干细胞中的作用尚未得到证实。在此，我们发现Oct-3/4在由神经干细胞和神经祖细胞组成的神经球（NS）中表达，并且通过腺病毒载体上调或下调Oct-3/4会影响细胞命运。Oct-3/4下调会加速祖细胞的神经元分化，而其持续表达则会阻止神经元分化。将神经球移植到成年大鼠脑内表明，Oct-3/4下调会促进体内NS细胞的分化。我们的研究结果表明Oct-3/4是NS细胞分化的重要调节因子，并提示调节Oct-3/4可能是NS细胞临床应用中的一种有用工具。
