RETINOIC ACID-TREATED P19 EMBRYONAL CARCINOMA-CELLS DIFFERENTIATE INTO OLIGODENDROCYTES CAPABLE OF MYELINATION

Retinoic acid treatment of P19 embryonal carcinoma cells induces their differentiation into cultures containing neurons and astrocytes. We p resent two lines of experimentation indicating that oligodendrocytes a lso develop from retinoic acid-treated P19 cells. We isolated an immor tal cell line from retinoic acid-treated P19 cell cultures whose proli feration is dependent upon epidermal growth factor. Upon removal of th e growth factor these cells differentiate into both astrocytes and oli godendrocytes as determined by immunostaining with antibodies to the a strocyte marker glial fibriliar acidic protein and the oligodendrocyte markers, myelin associated glycoprotein and 2', 3'-cyclic nucleotide 3'-phosphodiesterase. This cell line appears to be a bi-potential glia l precursor. We also found that oligodendrocytes developed directly fr om P19 cells when retinoic acid-treated cells were transplanted into t he brains of neonatal rat pups. Cells that developed into oligodendroc ytes migrated into fiber bundles up to several millimeters from the si te of the graft. These P19-derived oligodendrocytes appeared to myelin ate axons from host neurons. Thus, retinoic acid-treated P19 cells dif ferentiate into neurons, astrocytes and oligodendrocytes, the three ce ll types that normally develop from embryonic neuroectoderm, indicatin g that these cell cultures differentiate in a fashion closely resembli ng that of embryonic neuroectoderm.