Pluripotency of somatic cell hybrids between nullipotent and pluripotent embryonal carcinoma cells.

Abstract

Embryonal carcinoma (EC) cells are stem cells of teratocarcinomas. Many lines of EC cells can differentiate into a wide spectrum of cell types and are termed pluripotent. Some EC cell lines, however, cannot differentiate and are termed nullipotent. Nullipotent and pluripotent cells are both developmentally uncommitted but differ in their potential for differentiation. As a first step in analyzing this difference we asked whether pluripotent × nullipotent somatic cell hybrids could differentiate. The pluripotent EC cell line PSA-1 was fused with a ouabainresistant, hypoxanthine phosphoribosyltransferase-deficient subclone of the nullipotent embryonal carcinoma cell line F9. The developmental potential of nine independent hybrid clones was assayed in vivo. The tumors derived from these hybrid cell lines contained the same spectrum of differentiated tissue types found in tumors produced by the pluripotent parent. Control nullipotent × nullipotent somatic cell hybrids produced tumors containing only embryonal carcinoma tissue. The pluripotent phenotype therefore behaves in a dominant fashion in these somatic cell hybrids. One explanation for these results is that nullipotent F9 cells lack a critical function required for differentiation in vivo, and this function is supplied to the hybrids by the pluripotent parent.