Studying Nuclear Reprogramming with Cell Hybrids

Every cell in a mammal, other than odd exceptions (e.g. mature erythrocytes or lymphocytes with rearranged antigen receptors) contains a complete complement of the genetic information required to build another copy of the animal in question. However, the vast majority of adult cells are terminally differentiated with fixed patterns of gene expression, and for a long time it was thought to be impossible to reverse the linear, one-way process of differentiation (with concomitant restriction of gene expression patterns) to create a pluripotent embryonic cell from such a terminally differentiated precursor cell. More recently, the cloning from adult somatic cells of apparently normal individuals of several vertebrate species, most notably the creation of the sheep “Dolly” in 1997 (1 ), showed that reversal of this process of increasing specification can be achieved. The cloning of mammalian species is achieved by nuclear transfer (NT); therefore, we conclude that the nucleus of the somatic donor provides all of the genetic information required, and that the mammalian oocyte contains an activity that acts on the donor nucleus to reprogram an embryonic state. This reassignment of a cell’s nucleus from a somatic to an embryonic program is generally termed nuclear reprogramming (NR) and is a complex process that involves the restructuring of the chromatin in the nucleus, remodeling of DNA modifications (e.g. methylation), and a major change in gene expression patterns.