Embryonic hybrid cells: a powerful tool for studying pluripotency and reprogramming of the differentiated cell chromosomes

Abstract

The properties of embryonic hybrid cells obtained by fusion of embryonic stem (ES) or teratocarcinoma (TC) cells with differentiated cells are reviewed. Usually, ES-somatic or TC-somatic hybrids retain pluripotent capacity at high levels quite comparable or nearly identical with those of the pluripotent partner. When cultured in vitro, ES-somatic-and TC-somatic hybrid cell clones, as a rule, lose the chromosomes derived from the somatic partner; however, in some clones the autosomes from the ES cell partner were also eliminated, i.e. the parental chromosomes segregated bilaterally in the ES-somatic cell hybrids. This opens up ways for searching correlation between the pluripotent status of the hybrid cells and chromosome segregation patterns and therefore for identifying the particular chromosomes involved in the maintenance of pluripotency. Use of selective medium allows to isolate in vitro the clones of ES-somatic hybrid cells in which "the pluripotent" chromosome can be replaced by "the somatic" counterpart carrying the selectable gene. Unlike the TCsomatic cell hybrids, the ES-somatic hybrids with a near-diploid complement of chromosomes are able to contribute to various tissues of chimeric animals after injection into the blastocoel cavity. Analysis of the chimeric animals showed that the "somatic" chromosome undergoes reprogramming during development. The prospects for the identification of the chromosomes that are involved in the maintenance of pluripotency and its cis-and trans-regulation in the hybrid cell genome are discussed.

Human Embryonic Stem Cells Reprogram Myeloid Precursors Following Cell–Cell Fusion

“…The hybrid cells were near tetraploid, with an average chromosome number of 85.8 (n ϭ 55, SD ϭ 0.60). Chromosome loss during clonal expansion has frequently been reported in previous cellcell fusion experiments [33]. All the clones expressed EGFP (Figs.…”

Reprogramming in nuclear transfer

“…Cell-fusion experiments have revealed the molecular dominance and the reprogramming capabilities of embryonic cells compared to differentiated ones (for a recent review, see [4]). The molecular dominance of pluripotent embryonic stem (ES), embryonal carcinoma (EC) or embryonic germ (EG) cells is demonstrated by the repression of tissue-specific genes [5], de novo expression of the transcription factor Oct-4 by the somatic genome, reactivation of the previously inactivated X-chromosome, and specific demethylation of imprinted genes [6,7].…”

Reprogramación celular

“…Está comprobado que la reprogramación celular por transferencia nuclear (Wakayama et al, 1998) por fusión celular (Cowan et al, 2005) y por híbridos resultantes de células madre embrionarias con células somáticas (Serov et al, 2001) permite el restablecimiento del estado pluripotente de núcleos somáticos (Hochedlinger & Jaenisch, 2006). Los mecanismos mo-leculares de la reprogramación aun se están comprendiendo.…”