HYBRID CELL EXTINCTION AND REEXPRESSION OF OCT-3 FUNCTION CORRELATES WITH DIFFERENTIATION POTENTIAL

The Oct-3 gene is expressed in highly undifferentiated cells and is im plicated in mammalian early embryogenesis. We have generated a series of hybrid cells between pluripotent embryonal carcinoma cells (Oct-3+) and fibroblasts (Oct-3-), and have studied the regulation and functio n of Oct-3. Upon fusion, the hybrid cells differentiated to nestin+/Br n-2+ cells resembling neuroepithelial stem cells. Expression of Oct-3 was extinguished at the transcriptional level in all the hybrid cells examined. The Oct-3 modulating activity required for the Oct-3-mediate d enhancer activation was also extinguished. When the Oct-3 transactiv ating function was introduced into the hybrid cells, they transformed into morphologically distinct nestin-/Brn-2- cells ('revertants'). Whe n the 'revertant' cells subsequently lost Oct-3 expression, they diffe rentiated back to nestin+/Brn-2+ cells. The close correlation between the phenotypic changes and the gain/loss of Oct-3 function indicates t hat Oct-3 can induce dedifferentiation of the neural cells.