Embryonal Cell Hybrids: New Opportunities for Studying Pluripotency and Reprogramming of the Differentiated Cell Chromosomes

Here we study the properties of cell hybrids produced by the fusion of embryonal stem cells and differentiated ones. During in vitrocultivation, such hybrids predominantly lose the somatic partner chromosomes, although the loss of the embryonic partner autosomes is also common in the clones; i.e., this is a bidirectional process. The use of a selective media allows the isolation of the clones, with the embryonal X chromosome replaced by the somatic genome homolog. The cell hybrids with a near-diploid chromosome set preserve the high-level pluripotency properties of the embryonal partner including the capacity to form chimeras after their introduction in the blastocoel. An investigation of the chimeric animals demonstrated a reprogramming of the “somatic” X chromosome in the course of development. The prospective identification of the chromosomes involved in the maintenance of pluripotency and studies of its cis-and trans-regulation in the cell hybrid genome are discussed.