Hybrids of pluripotent and nullipotent human embryonal carcinoma cells: Partial retention of a pluripotent phenotype

To investigate whether the failure of human EC cells that do not differenti ate is due to the loss of key differentiation-permissive functions or the a cquisition of specific inhibitory functions, we tested the ability to diffe rentiate of 2 hybrids produced between a relatively nullipotent human EC ce ll line, 2102Ep, and a pluripotent human EC cell line NTERA2, Both hybrids, which exhibited an EC phenotype, were able to differentiate readily in res ponse to retinoic acid. Furthermore, 1 hybrid produced a well-differentiate d xenograft tumor, which contained, like the NTERA2 tumors, glandular struc tures, loose mesenchymal tissues and nodules of cartilage, after injection into a SCID mouse. Thus, the failure of 2102Ep EC cells to differentiate is recessive and due to the loss of a key gene function or functions. Neverth eless, the hybrids differed from the pluripotent NTERA2 line by failing to differentiate in neurons, indicating that 2102Ep cells also had acquired a specific, dominantly-acting, inhibitory mutation specific to the neural lin eage. Furthermore, the expression of collagen II by one hybrid before and a fter induction with retinoic: suggested a propensity for spontaneous differ entiation not evident in the parental NTERAZ cells. Thus, the mechanisms th at restrict the differentiation capacity of the nullipotent 2102Ep line are complex and include both recessive and dominant acting factors. (C) 2001 W iley-Liss, Inc.