The developmental programs of somatic cells are characterized by remarkably stable patterns of gene expression and repression. Nonetheless, through nuclear reprogramming, the developmental programs of somatic cells may be erased and redirected 
. In recent years, much attention has been given to nuclear reprogramming of somatic cells in hopes of generating patient-specific embryonic stem cells (ESCs) that might provide valuable tools for basic science studies and potential novel therapeutics 
Nuclear reprogramming was first demonstrated as an integral part of mammalian development; following fusion of the egg and sperm, the fused gametic nucleus must be reprogrammed, through a series of changes that include DNA demethylation and chromatin remodeling, to that of an embryonic cell if development is to be successful 
. In methods such as somatic cell nuclear transfer (SCNT), the nucleus of a somatic cell is transferred to an enucleated oocyte for reprogramming to an embryonic cell state, through the use of the endogenous machinery 
. Methods other than SCNT have also been used to reprogram somatic cells including fusion with ESCs and genetic reprogramming via co-expression of pluripotency-associated genes 
. Each of these methods has advantages and limitations. For example, although SCNT takes advantage of endogenous programs, it requires the use of oocytes that may be in short supply 
. In the case of cell fusion, although the cells are in great supply, the procedure results in the formation of tetraploid cells that are genetically unstable 
. Finally, although genetic reprogramming by co-expression of the stem cell factors Oct4, Sox2, c-myc and Klf4 is remarkable in that it yields ESCs capable of contributing to both the somatic and germ cell lineages, use of the reprogrammed cells to generate offspring results in increased tumorigenesis in progeny 
. Moreover, in all methods, the efficiency of reprogramming is very low, suggesting that additional components of the reprogramming pathways remain to be identified.
In this study, we sought to optimize cell fusion reprogramming protocols, based on fusion of somatic cells and ESCs, in order to screen for enhancers of somatic cell reprogramming. We reasoned that if a factor functions in reprogramming, overexpression of that factor in somatic cells might increase the efficiency with which the cells can be reprogrammed. Thus, we tested whether overexpression of the following factors, individually, increased reprogramming efficiency of MEFs: Oct4, Nanog, Sox2, and Sall4.