UTF1 deficiency promotes retinoic acid-induced neuronal differentiation in P19 embryonal carcinoma cells

UTF1 (undifferentiated embryonic cell transcription factor 1) is a marker for the pluripotency of embryonic stem cells. We found that UTF1-deficient clones, which were isolated from P19 embryonal carcinoma (EC) cells, showed higher neuron-differentiating potentials than the parental cell line. Consistent with this result, suppression of UTF1 expression in P19 cells by RNA interference enhanced retinoic acid (RA)-induced neuronal differentiation. Moreover, reconstitution of UTF1 expression in UTF1-deficient clones decreased their ability to undergo neuronal differentiation. Interestingly, the growth rates of UTF1-deficient P19 cells did not differ from that of parental cells in adherent cultures, but were increased in embryoid bodies during RA-induced differentiation. Furthermore, different from the parental cells, UTF1-deficient P19 clones could proceed to neuronal differentiation without forming embryoid bodies. Based on these results we proposed that endogenous UTF1 prevented P19 EC cells from neuronal differentiation, and that the loss of UTF1 directed EC cells toward the neuronal fate.