Nuclear reprogramming of cells

Nuclear reprogramming describes a switch in gene expression of one kind of cell to that of another unrelated cell type. Early studies in frog cloning provided some of the first experimental evidence for reprogramming. Subsequent procedures included mammalian somatic cell nuclear transfer, cell fusion, induction of pluripotency by ectopic gene expression, and direct reprogramming. Through these methods it becomes possible to derive one kind of specialized cell (such as a brain cell) from another, more accessible, tissue (such as skin) in the same individual. This has potential applications for cell replacement without the immunosuppression treatments that are required when cells are transferred between genetically different individuals. This article provides some background to this field, a discussion of mechanisms and efficiency, and comments on prospects for future nuclear reprogramming research. As a fertilized egg develops into an adultorganism, specialized cells are formedby a one-way process, and they become increasingly, and normally irreversibly, com-mitted to their fate. A skin cell does not naturally turn into, or give rise to, a brain cell, nor does an intestine cell generate a heart cell. Nevertheless, there are certain experimental procedures that enable just these kinds of changes to take place. They entail nuclear reprogramming, a term that describes a switch in nuclear gene expression of one kind of cell to that of an embryo or other cell type. This process is of interest for three reasons. First, identifying how reprogramming takes place can help us understand how cell differentiation and specialized gene expression are normally maintained. Second, nuclear reprogramming represents a first major step in cell-replacement therapy, in which defective cells are replaced by normal cells of the same or a related kind but derived from a different cell type. Eventually, it may be possible to derive replacement heart, pan-creas, or other types of cells from the skin of the same individual, thereby avoiding the need for im-munosuppression. Third, nuclear reprogramming enables the culture of lines of cells from diseased tissues, and hence allows us to analyze the nature of the disease and to screen for therapeutic drugs. We review these procedures, discuss the mech-anisms that may be involved, and comment on prospects in this field