Altered differentiation, indefinite growth potential, diminished tumorigenicity, and suppressed chimerization...

Hybrids between normal mouse thymocytes and a hypoxanthine-guanine phosphoribosyl transferase (HGPRT) -deficient, pseudodiploid, multipotent mouse teratocarcinoma cell line displayed predominately hypotetraploid modes with differential patterns of karyotypic variation and no apparent consistent pattern of chromosome segregation. The hybrids failed to express thymocyte antigens Thy-1.2, Lyt-1, and Lyt-2, indicating suppression of thymocyte differentiation. Like the teratocarcinoma parent, the hybrids had an embryonal carcinoma (EC) stem cell component which exhibited indefinite growth potential in vitro and produced tumors with multiple pathways of tissue differentiation when injected subcutaneously. Hybrids had decreased proportions of EC cells and individually unique patterns of differentiation. The tumorigenicity of hybrids was diminished, indicating partial suppression of the neoplastic phenotype by the genome of the thymocyte parent. The EC parent gave chimerization frequencies of 18.5-19.2%, confirming the findings of Dewey et al. that mutant teratocarcinoma cells can be used to synthesize chimeric mice. "Selfed" near-tetraploid EC cells gave a frequency of 2.3%, showing that an increase in ploidy can reduce, although not eliminate, chimerization potential. No chimeras could be detected with hybrids (frequency less than 0.65%). Thus, there was no evidence that a thymocyte could be "reprogrammed" to participate in new developmental pathways.